Research and Clinical Trials

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Join a Clinical Trial at the Nantz National Alzheimer Center

Treatment trials currently enrolling participants

Pre-symptomatic Alzheimer’s disease Mild cognitive impairment due to Alzheimer’s disease
Mild to moderate Alzheimer’s disease
Frontotemporal dementia with progranulin mutations Schizophrenia-spectrum disorders

Active treatment trials, but not currently enrolling participants

Join a Research Study

Completed Studies

 

For more information, please contact Clinical Research Coordinator Jennifer Garrett, RN, at jmgarrett@houstonmethodist.org or call 281.222.9983.

 

 


Pre-symptomatic Alzheimer’s disease

 

 

Phase 3 Placebo-Controlled Study of BAN2401 (Lecanemab) in Subjects with Preclinical AD (AHEAD) Study

TThe primary purpose of this study is to determine whether treatment with lecanemab (BAN2401) is superior to placebo on change from baseline of the Preclinical Alzheimer Cognitive Composite 5 (PACC5) at 216 weeks of treatment (A45 Trial) and to determine whether treatment with lecanemab is superior to placebo in reducing brain amyloid accumulation as measured by amyloid positron emission tomography (PET) at 216 weeks of treatment (A3 Trial).

  • Study director (local PI): Joseph C. Masdeu, MD, PhD
  • Sponsor: Eisai Inc..
  • Recruiting?: Yes
  • Official study title: AHEAD 3-45 Study: A Placebo-Controlled, Double-Blind, Parallel-Treatment Arm, 216 Week Study to Evaluate Efficacy and Safety of Treatment With BAN2401 in Subjects With Preclinical Alzheimer's Disease and Elevated Amyloid (A45 Trial) and in Subjects With Early Preclinical Alzheimer's Disease and Intermediate Amyloid (A3 Trial).
  • ClinicalTrials.gov identifier: NCT04468659
  • Conditions studied: Preclinical Alzheimer’s Disease and Early Preclinical Alzheimer’s Disease
  • Intervention Drugs: Lecanemab (BAN2401) in comparison with placebo
  • Study Type: Interventional
  • Phase: Phase 3
  • Duration of participation:The expected time the subject will be in the study is about 4.5 years
  • IRB #: Pro00025015
  • IRB approval date: 5/26/20

Eligibility
Inclusion criteria: 

-Individuals of either sex, 55-80 years of age.
Those 55 to 64 must have 1 of the following additional risk factors, given the relatively low rates of amyloid positivity less than (<) 65 years:
  • First degree relative diagnosed with dementia onset before age 75, or
  • Known to possess at least 1 apolipoprotein E4 variant (APOE4) allele, or
  • Known before screening to have elevated brain amyloid according to previous PET or cerebrospinal fluid (CSF) testing. Individuals with historical amyloid PET scans with intermediate brain amyloid (example, from preclinical Alzheimer's disease (AD) studies such as A4 or EARLY) are eligible to be screened, provided the participant did not participate in any clinical studies involving anti-amyloid therapies subsequent to the PET assessment

-Global Clinical Dementia Rating (CDR) score of 0 at screening
-Mini Mental State Examination score greater than or equal to (>=) 27 at screening
-A45 Trial: Elevated brain amyloid pathology by amyloid PET
-A3 Trial: Intermediate levels of brain amyloid pathology by amyloid PET

Exclusion criteria: 
Participants who meet any of the following criteria will be excluded from this study:

  • Females who are breastfeeding or pregnant at screening or baseline
  • Females of childbearing potential who within 28 days before study entry, did not use a highly effective method of contraception
  • History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of screening
  • Current or history within the past 2 years of psychiatric diagnosis or symptoms that, in the opinion of the investigator, could interfere with study procedures
  • Contraindications to 3 Tesla magnetic resonance imaging (MRI) scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (example, in-skull and cardiac devices other than those approved as safe for use in MRI scanners), or exhibit other significant pathological findings on brain MRI at Screening
  • Hypersensitivity to any monoclonal antibody treatment
  • Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study
  • Bleeding disorder that is not under adequate control (including a platelet count <50,000 or international normalized ratio [INR] >1.5) at screening
  • Results of laboratory tests conducted during screening that are outside the following limits:
    • Thyroid stimulating hormone (TSH) above normal range
    • Abnormally low (below lower limit of normal [LLN]) serum vitamin B12 levels for the testing laboratory (if participant is taking vitamin B12 injections, level should be at or above the LLN for the testing laboratory). A low vitamin B12 is exclusionary, unless the required follow-up labs (homocysteine and methylmalonic acid [MMA]) indicate that it is not physiologically significant
  • Known to be human immunodeficiency virus (HIV) positive
  • Any other clinically significant abnormalities that in the opinion of the investigator require further investigation or treatment or may interfere with study procedures or safety
  • Malignant neoplasms within 3 years of screening (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer in male participants with treatment cycles completed at least 6 months before screening). Participants who had malignant neoplasms but who have had at least 3 years of documented uninterrupted remission before screening need not be excluded
  • Answer "yes" to Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation Type 4 or 5, or any suicidal behavior assessment within 6 months before screening, at screening, or at baseline, or has been hospitalized or treated for suicidal behavior in the past 5 years before screening
  • Known or suspected history of drug or alcohol abuse or dependence within 2 years before screening or a positive urine drug test at screening. Participants who test positive for benzodiazepines, opioids, or tetrahydrocannabinol (THC) in urine drug testing need not be excluded unless in the clinical opinion of the investigator this is due to potential drug abuse
  • Taking prohibited medications
  • Participation in a clinical study involving:
    • Any anti-amyloid immunotherapy (example, therapeutic monoclonal antibody or active anti-amyloid vaccine) at any time, unless it can be documented that the participant was randomized to placebo or never received study drug
    • Any immunoglobulin therapy, or vaccine within 6 months before Screening, unless it can be documented that the participant was randomized to placebo or never received study drug
    • Lecanemab
    • Any new chemical entities or investigational drug for AD within 6 months before screening unless it can be documented that the participant received only placebo
    • Any other investigational medication or device study in the 8 weeks or 5 half-lives (whichever is longer) of the medication before randomization unless it can be documented that the participant was in a placebo treatment arm
  • Planned surgery during the screening phase or within 3 months of screening, which requires general anesthesia

What is involved?

Testing and Procedures: History, Clinical and Neurological Examination, Psychological testing, questionnaires about your quality of life, ECGs (electrocardiograms), Magnetic Resonance Imaging (MRI) scans, amyloid PET scans, Tau PET scans, blood and urine specimen collection, vital signs, disclosure of your amyloid imaging results, and study drug administrations (intravenous infusions).

Frequency of visits:
-Screening period – 6 visits
-Treatment phase:
  • A3 study participants: The Study Treatment Period will last for about 4 years.  During this period, you will come into the clinic every 4 weeks for up to 54 visits. Thirty-four (34) of these visits will be “infusion only” visits.  The other 20 visits will be longer, study visits.
    • Infusion Only Visits: At these visits, you will have the infusion of study drug (or placebo). This will only take about an hour to complete.
    • Study Visits: At these visits, which occur about every third trip to the clinic, we will collect information about your memory and ability to perform certain tasks to see how you are doing on study drug (or placebo).  After completing these tasks, you will have an infusion. These visits will take about 3-5 hours to complete.
  • A45 study participants: The Study Treatment Period will last for about 4 years.  During this period, you will come into the clinic every 2 weeks for the first 96 weeks (a little less than 2 years), and then every 4 weeks until the end of the study, for up to 78 visits.  Fifty-eight (58) of these visits will be “infusion only” visits.  The other 20 will be longer study visits. 
    • Infusion Only Visits:  At these visits, you will have the infusion of study drug (or placebo). This will only take about an hour to complete. 
    • Study Visits: At these visits we will collect information about your memory and ability to perform certain tasks to see how you are doing on study drug (or placebo).  After completing these tasks, you will be have an infusion. These visits will take about 3-5 hours to complete.
-In addition to the scheduled visits, the study doctor may ask you to come in for additional visits called Unscheduled Visits, when the study doctor feels that you will need to come back to the clinic for safety reasons. 
  • Follow-up period – About 3 months after the Study Treatment period is completed, you will return to the clinic for a follow-up visit. The follow-up visits can be split up across multiple days.
Costs:  No costs will be charged for any of the study procedures. To compensate the time, you take to undergo the procedures in this study, you will receive $50 for each completed study-related visit. You will also receive $50 for each completed amyloid PET scan, tau PET scan and MRI scan.

 

 

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Mild cognitive impartment due to Alzheimer's disease

 

 

Glutathione in Mild Cognitive Impairment

The goal of this study is to evaluate potential improvement in cognition from ingesting proteins N-acetylcysteine and glycine every day for 12 weeks.  It also seeks to evaluate potential improvement in the efficiency of the body to process glucose, lower oxidative stress and improve endothelial function.

  • Study director (local PI): Rajagopal Viswanath Sekhar, MD, BS
  • Co-Investigator: Joseph C. Masdeu, MD, PhD
  • Sponsor: NIH: National Institute of Health
  • Recruiting?: Yes
  • Official study title:  Glutathione in Mild Cognitive Impairment
  • ClinicalTrials.gov identifier:  NCT03493178
  • Conditions studied: Mild Cognitive Impairment (MCI)
  • Intervention Drugs: Glutathione, N-acetylcysteine and glycine
  • Study Type: Observational
  • Study Phase: N/A
  • Duration of participation: The expected time the participant will be in the study is approximately 6 months. 
  • IRB #: Pro00018465
  • IRB approval: 12/27/2017

Eligibility

Inclusion criteria: 

  • Participants must be between 55 and 85 years of age and have cognitive impairment.
  • Cease over the counter health supplements for 6 months
  • Must speak English or Spanish fluently.

Exclusion criteria:

  • Hospitalization within the last 3 months
  • Known diabetes or liver disease
  • History of stroke, brain tumor or active treatment for heart failure
  • History of psychiatric disorders or untreated depression

What is involved?

  • Testing and Procedures: Physical and neurological examination, cognitive testing, blood and urine tests, vital signs and patient history, medication by pills, metabolic testing, endoPAT, fasting required
  • Frequency of visits: There are 7 planned clinic visits during the study over approximately 6 months including the following:
    • 1 screening visit for evaluation of screening tests for enrollment.
    • 6 additional outpatient visits (intervals are variable based on screening). 
Costs: There are no costs associated with participation in the study.  A $150 stipend will be provided to help cover your expenses related to the study after visit 3 and visit 6.  A $200 stipend will be provided after visit 7.  You will receive the checks by mail from Baylor College of Medicine.

 

 

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Mild cognitive impartment due to Alzheimer's disease

 

 

Memory Improvement through Nicotine Dosing (MIND) Study

The purpose of the study is to see if daily transdermal nicotine is able to produce a significant cognitive, clinical and functional improvement in participants with MCI. Neuronal nicotinic receptors have long been known to play a critical role in memory function in preclinical studies, with nicotine improving attention, learning, and memory function.
Summary

  • Study director (local PI): Joseph C. Masdeu, MD, PhD
  • Sponsor:  National Institute on Aging (NIA)
  • Recruiting?: Yes
  • Official study title: Long-Term Nicotine Treatment of Mild Cognitive Impairment.
  • ClinicalTrials.gov identifier: NCT02720445
  • Conditions studied: Mild Cognitive Impairment
  • Intervention Drugs: Nicotine Transdermal patch and control placebo patch. Study drug (nicotine patches or matching placebo patches) will be worn during waking hours.
  • Study type: Interventional
  • Phase: Phase 2
  • Duration of participation: The expected time the subjects will be in this study is approximately 2 years.
  • IRB #: Pro00016502
  • IRB approval date: 4/19/2017

Eligibility
Inclusion criteria: 

  • Participant must have a subjective memory concern as reported by participant, study partner, or clinician
  • Abnormal memory function documented by scoring within the education adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall) from the Wechsler Memory Scale-Revised:
    • Less than or equal to 11 for 16 or more years of education
    • Less than or equal to 9 for 8 - 15 years of education
    • Less than or equal to 6 for 0 - 7 years of education
  • Mini-Mental State Exam score between 24 and 30, inclusive
  • Clinical Dementia Rating (CDR) Global = 0.5. Memory Box score must be at least 0.5
  • General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer’s disease dementia cannot be made by the site clinician at the time of the screening visit
  • Age 55-90 (inclusive)
  • Stable permitted medications for 4 weeks or longer as specified in Section 6.10, including:
    • Memantine is allowable if stable for 12 weeks prior to screen
  • Geriatric Depression Scale score of less than or equal to 9
  • Study Partner is available who has frequent contact with the subject (e.g. an average of 10 hours per week or more), and can accompany the participant to most visits to answer questions about the participant
  • Adequate visual and auditory acuity to allow neuropsychological testing
  • Good general health with no additional diseases/disorders expected to interfere with the study
  • Participant is not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile)
  • Completed six grades of education or has a good work history
  • Must speak English fluently

Exclusion criteria: 

  • Any use of tobacco or nicotine products within the past year, such as smoking cigarettes, pipes, cigars, etc.) or use of other nicotine products (chewing tobacco, e-cigarettes, nicotine patches, gum, sprays, etc.).
  • Any significant neurologic disease such as Alzheimer’s disease dementia, Parkinson’s disease, multi-infarct dementia, Huntington’s disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.
  • Major depression, bipolar disorder as described in DSM-V within the past 1 year or psychotic features, agitation or behavioral problems within 3 months, which could lead to difficulty complying with the protocol
  • History of schizophrenia (DSM V criteria)
  • History of alcohol or substance abuse or dependence within the past 2 years (DSM V criteria)
  • Clinically significant or unstable medical condition, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results, or the subject’s ability to participate in the study.
  • Has had a history within the last 5 years of a primary or recurrent malignant disease with the exception of non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen post-treatment
  • Clinically significant abnormalities in B12 or TFTs that might interfere with the study. A low B12 is exclusionary unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.
  • Clinically significant abnormalities in screening laboratories or ECG.
  • Residence in a skilled nursing facility.
  • Use of any excluded medication as described in Section 6.10, including:
    • Use of cholinesterase inhibitors or centrally acting pro- or anticholinergic drugs
    • Use of any investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to screening.
  • For CSF sub-study participants, a current blood clotting or bleeding disorder, or significantly abnormal PT or PTT at screening
  • For MRI sub-study participants, contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or cardiac pacemaker.
  • Participants whom the Site PI deems to be otherwise ineligible.

What is involved?

  • Testing and procedures: Neurological and physical examinations, cognitive testing and thinking skills tests (both written – using a paper and pen, and on electronic device like a computer or iPad), Behavioral tests, ECG, blood (for routine laboratory tests, genetic testing, biomarker research tests, and to measure level of nicotine in your blood) and urine specimen collection, vital signs, Study drug dispensation and, Research Satisfaction Survey.
  • Frequency of visits:
    • Total 12 visits including:
      • Screening visit:  ( 3-5 hours)
      • Baseline period:  Total 5-6 hours over the course of 2 days
      • 10 Visits during “treatment period”:   (1-4 hours each)
  • Costs: No costs will be charged for any of the study procedures. The study will cover the cost of all assessments, the nicotine patch, and tests related to the study. Subjects will receive $50 to help pay for gas and time coming to the visit. 

 

 

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Mild to moderate Alzheimer's disease

 

 

Glutathione and Alzheimer’s Disease

Alzheimer's disease (AD) is associated with significant, progressive cognitive decline. Key defects in mitochondrial fuel metabolism insulin resistance, inflammation and decreased brain glucose uptake are linked to AD. This trial will investigate the effects of supplementing glycine and N-acetylcysteine vs. alanine as placebo on these defects in AD and examine the effects on cognition.
Glutathione (GSH) deficiency, oxidative stress, mitochondrial dysfunction, insulin resistance and inflammation are linked to Alzheimer's disease (AD). In prior studies, investigators have shown that GSH deficiency contributes to mitochondrial impairment and oxidative stress, and that GSH deficiency can be corrected by supplementing its precursors glycine and cysteine (provided as N-acetylcysteine, NAC), with the combination termed GlyNAC.
This randomized clinical trial will evaluate the effect of GlyNAC vs. alanine placebo supplementation provided for 24-weeks to patients with AD, and measure changes in cognition, GSH concentrations, oxidative stress, brain glucose uptake, brain inflammation and insulin resistance.
  
  • Study director (local PI): Joseph C. Masdeu, MD, PhD
  • Sponsor: This study is being sponsored by Baylor College of Medicine (BCM) and is funded by grants from the National Institute on Aging (NIA)
  • Recruiting?: Yes
  • Official study title: Glutathione, Brain Metabolism and  Inflammation in Alzheimer’s Disease
  • ClinicalTrials.gov identifier:  NCT04740580
  • Conditions studied: Alzheimer’s Disease (AD).
  • Intervention Drugs: Glutathione, N-acetylcysteine and glycine
  • Study Type: Interventional Study
  • Study Phase: Early Phase 1
  • Duration of participation: : The expected time the subject will be in the study is around 24 weeks.
  •  IRB #: Pro00030030
  • IRB approval: 1/12/2022

Eligibility
Inclusion criteria: 

  • Individuals of either sex, 55-85 years of age .
  • Gradual and progressive memory loss for more than 1 year, with a Montreal   Cognitive Assessment score of 10-20.
  • Tau positivity on PET scan.
  • Availability of a study partner.

Exclusion criteria: 
All participants must not meet the following criteria:

  • Hospitalization in past 3 months
  • Known diabetes or use of anti-diabetic medications
  • Untreated thyroid disease
  • Creatinine levels > 1.5 mg/dL
  • Hemoglobin concentration < 11.0 g/dL
  • Known liver disease, or AST/ALT level >2x upper limit of normal
  • History of stroke, brain tumor, active heart failure or active cancer (removable basal cell cancers will not be an exclusion criteria)
  • Untreated depression or other severe psychiatric disorders
  • Pregnancy or nursing. Although unlikely in this population, all women of childbearing potential will have a pregnancy test to exclude pregnancy, at screening and before each pet procedure.

What is involved?

  • Testing and Procedures: History, Clinical and Neurological Examination,  Psychological testing,  Brain MRI scan (without contrast), one tau PET scan, two inflammation PET scans, two brain metabolism PET scans, arterial line placement,  calorimetry, blood specimen collection (for biochemical studies), and vital signs
  • Frequency of visits:
      • Recruitment visit (at Houston Methodist) – 1
      • Screening visit (at BCM) –  1
      • Cognitive and Metabolic evaluation visits (at BCM) – 3
      • Imaging (MRI and PET scan) visits (at Houston Methodist) – 3  
  • Costs: No costs will be charged for any of the study procedures. To compensate the time, you take to undergo the procedures in this study, you will receive $50 for the MRI study,  and  $150 per PET study . There are 5 PET scans and 1 MRI scan per participant. Total $800 will be paid for scans. In addition, Baylor College of Medicine will pay $300 for metabolic/cognition visits + $100 for mini-visits. Therefore, total $1200 will be paid for complete study participation.   These payments will be made as follows:
      • After completing visits 1-3: $200 (1 MRI scan, 1PET scan).
      • After completing visits 4-7: $400 (2 PET scans, 1 Metabolic study).
      • After completing visits 8-10: $200 (1 Metabolic study, 4 mini-studies).
      • After completing visits 11-12: $400 (1 Metabolic study, 2 PET scans)

These payments will made by ClinCard by Baylor's accounts office and will require a copy of the subject's social security card to do this.

 

 

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Mild to moderate Alzheimer's disease

 

 

Treatment of Inflammation in Alzheimer’s Disease

This is a research study to find out if an immunomodulatory drug called Interleukin-2 (IL-2) is safe and has potential efficacy in Alzheimer disease.
  • Study director (local PI):  Alireza Faridar, MD
  • Sponsor: Houston Methodist Research Institute
  • Recruiting?: Yes
  • Official study title: A Phase II Clinical Trial of Interleukin-2 (IL-2) in Patients with Mild to Moderate Alzheimer’s Disease Progress.
  • Conditions studied: Mild to moderate Alzheimer’s disease
  • Intervention Drugs: Interleukin-2 (IL-2) compared with a placebo. The study drug will be given subcutaneously.
  • Study Type: Interventional
  • Study Phase: 2
  • Duration of participation: The expected time the subject will be in the study is about 30 weeks.
  •  IRB #: Pro00030798
  • IRB approval: 5/27/2021
Eligibility
Inclusion criteria:
  • Individuals of either sex, 55-86 years of age.
  • Mini Mental State Examination score between 12 and 26 (inclusive) at baseline.
  • Ability of the participant or their informant/study partner and/or legally authorized representative to understand the purpose and risk and provide a signed and dated informed consent
  • Must speak English fluently.

Exclusion criteria: 
All participants must not meet the following criteria:

  • Serious, active bacterial, fungal or viral infection, active or latent tuberculosis.
  • History of severe pulmonary (lung) dysfunction.
  • Abnormal liver function tests.
  • Severe cardiac dysfunction.
  • Hypersensitivity or allergy to IL-2.
  • History of hemorrhage or large infract, brain tumors, or any significant brain pathology.
  • Hospitalization or change of chronic concomitant medication within one month prior to screening.
  • History of bowel ischemia/perforation, or GI bleeding requiring surgery.
  • Clinically significant, advanced, or unstable heart, ling, kidney, liver, endocrine of metabolic disease that may interfere with study participation
  • History of cancer within 3 years of screening with the exception of fully removed non-melanoma skin cancers of non-metastatic prostate cancers.
  • History of acute/chronic hepatitis B or C.
  • Any other clinically significant abnormalities that in the opinion of the investigator require further investigation or treatment or may interfere with study procedures or safety
  • Contraindications to or intolerance of oral or IV corticosteroids.
What is involved?
  • Testing and Procedures: History, Clinical and Neurological Examination,  ECGs (electrocardiograms), spinal tap, blood specimen collection (for safety labs, APOE genetic test and immune analysis), and vital signs, The study drug (IL-2 or placebo) will be given subcutaneously.
  • Frequency of visits:
      • Screening phase – 1 visit
      • Treatment phase – 10 visits
      • Follow-up phase – 2 visits 
Costs: No costs will be charged for any of the study procedures. The  study drug, all study procedures and assessment will be paid for by the study funds. Participants will not be paid for their participation in the study, but study team will provide a parking voucher for each study visit.

 

 

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Frontotemporal dementia with progranulin mutations



Anti-Sortilin Antibody (AL001) in Frontotemporal Dementia

This study seeks to evaluate the efficacy and safety of AL001 in subjects with a progranulin gene mutation that causes frontotemporal dementia. The purpose of this study is to evaluate the clinical effects, safety, and tolerability of AL001 compared with placebo in carriers of a progranulin gene mutation causative of FTD. AL001 is an immunotherapy (antibody drug) designed to bind to the Sortilin protein and increases progranulin levels by blocking its degradation.
  • Study director (local PI): Joseph C. Masdeu, MD, PhD
  • Sponsor: Alector, Inc.
  • Recruiting?: Yes
  • Official study title: A Phase 3, Multicenter, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of AL001 in Individuals at Risk for or With Frontotemporal Dementia Due to Heterozygous Mutations in the Progranulin Gene
  • ClinicalTrials.gov identifier: NCT04374136
  • Conditions studied: Frontotemporal Dementia
  • Intervention Drugs: AL001 (a monoclonal antibody) and placebo control. Study drug (AL001 or placebo) will be administered every 4 weeks as an intravenous infusion over approximately 60 minutes, every 4 weeks for 48 weeks (symptomatic participants) or 96 weeks (pre-symptomatic participants).
  • Study Type: Interventional
  • Phase: Phase 3
  • Duration of participation: The expected time the subject will be in the study is 1 – 2 years. At the end of the treatment period, eligible subjects who completed the 48- or 96-week treatment period may enter a planned separate extension study for extended treatment.
  • IRB #: Pro00026293
  • IRB approval date: 8/17/2020

Eligibility
Inclusion criteria: 

  • Persons with a progranulin gene mutation and at risk of developing FTD symptoms as evidenced by a biomarker, or persons with a progranulin gene mutation and diagnosed with FTD.
  • If symptomatic, one of the criteria for the diagnosis of probable behavioral variant FTD, or FTD-semantic subtype or FTD-Progressive nonfluent aphasia.
  • Study partner who consents to study participation and who cares for/visits the participant daily for at least 5 hours per week.
  • Written informed consent must be obtained and documented (from the participant or, where jurisdictions allow it, from their legal decision maker).

Exclusion criteria: 

  • Dementia due to a condition other than FTD including, but not limited to, Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, Huntington disease, or vascular dementia.
  • Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
  • Current uncontrolled hypertension, diabetes mellitus or thyroid disease. Clinically significant heart disease, liver disease or kidney disease. History or evidence of clinically significant brain disease other than FTD.
  • Females who are pregnant or breastfeeding, or planning to conceive within the study period.
  • Any experimental vaccine or gene therapy.
  • History of unresolved cancer.
  • Current use of anticoagulant medications (e.g., coumadin, heparinoids, apixaban).
  • Residence in a skilled nursing facility, convalescent home, or long term care facility at screening; or requires continuous nursing care.

What is involved?

  • Procedures: Eligible subjects will be randomized to the AL001 dose (60 mg/kg) or placebo in a 2:1 ratio. Subjects will receive the study drug (or placebo) infusion every 4 weeks for 48 weeks (symptomatic participants) or 96 weeks (pre-symptomatic participants). Subjects will also have following procedures: Brain MRIs, optional lumbar punctures, neurological and physical examinations, cognitive testing and questioning, ECGs, blood specimen collection, vital signs
  • Frequency of visits:
      • Up to 6 weeks screening period
      • Visits once every 4 weeks for 48 or 96 weeks (“treatment period”)
      • Follow-up period of approximately 8 weeks
      • Eligible subjects will be enrolled into the treatment period on Day 1 and receive their first infusion of the study drug. Subjects will return to the study site every 4 weeks for their study drug infusion, blood collection, study procedures and assessments.
  • Costs: No costs will be charged for any of the study procedures. Subjects will be reimbursed as follows:
    • In reimbursement for travel and meals costs, you and your study partner will receive $50 each for attending all required study visits. You and your study partner will be paid after you have completed each visit.
    • You and your study partner may be reimbursed up to $200 for travel expenses (mileage/bus/train/taxi fares/flights/hotels/meals). You will be reimbursed for such costs after receipts have been received for these expenses. If these expenses are more than $200, they study team will need to get pre-approval from the Study Sponsor.

For more information, please contact clinical research coordinator Jennifer Garrett, RN, at jmgarrett@houstonmethodist.org or call 281.222.9983. 

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Schizophrenia-spectrum disorders

 

Ocrelizumab for Psychoses by Autoimmunity (OPA trial)

Some people who have what doctors currently call schizophrenia or bipolar disease may actually have a brain disease caused by auto-antibodies. Auto-antibodies are produced when the normal defense mechanism of the body goes wrong and begins to attack the body, like "friendly fire." Auto-antibodies attack brain receptors and then the person who has this problem begins to have hallucinations and other manifestations of schizophrenia, like feeling that people can see what they are thinking and also feeling that other people do not like them. If this disease is caused by auto-antibodies, typically the person is well until they are 15 years of age or older, but seldom older than 35 years. Then, in a matter of a few months they begin to have hallucinations and the other symptoms. Doctors still do not know whether some people with schizophrenia or bipolar disease have auto-antibodies attacking their brain. For this reason, in this study some of these patients will receive a treatment that suppresses the auto-antibodies and their symptoms after treatment will be compared with the symptoms of a group of similar patients who are given a preparation that looks like the real treatment, but it is not.

  • Study director (local PI): Joseph C. Masdeu, MD, PhD
  • Sponsor: Houston Methodist Research Institute with support (medication) from Genentech
  • Recruiting?: Yes
  • Official study title: Ocrelizumab for psychoses possibly caused by synaptic autoimmunity.
  • ClinicalTrials.gov identifier: NCT03971487
  • Conditions studied: Schizophrenia-spectrum psychosis
  • Intervention Drugs: Ocrelizumab in comparison with placebo
  • Phase: Phase 1
  • Duration of participation: The expected time the subject will be in the study is between 18 to24 months
  • IRB #: Pro00021901
  • IRB approval date: 7/30/2019

Eligibility
Inclusion criteria: 

  • Individuals of either sex, 18-35 years of age.
  • Having an active psychotic disorder meeting DSM-5 criterion, including a duration of at least six months, for Schizophrenia Spectrum Disorder, as defined by the Mini International Neuropsychiatric Interview (MINI).
  • A total PANSS ≥ 60 and a score ≥ 4 on at least 2 of the PANSS positive symptoms.
  • Normal academic performance at least until the age of 15 years and absence of psychiatric symptoms before the same age.
  • Ability to assent or consent to the performance of the study and participate in testing procedures.
  • Participants must have received a full COVID-19 vaccine at least three weeks before the first infusion of the study drug.

Exclusion criteria: 

  • The dose of antipsychotic medication (if they are on one) has been changed less than two weeks prior to baseline PANSS testing (Visit 2, see below).
  • Patient treated with a medication designed to suppress the immune system, other than standard analgesics or antipyretics, in the six months prior to randomization.
  • Vaccinated with a live-attenuated vaccine less than 4 weeks before ocrelizumab infusion or with a non-live vaccine less than 2 weeks before infusion.
  • Active infection, or history of or known presence of recurrent or chronic infection (for example, hepatitis B or C, Human Immunodeficiency Virus, syphilis, tuberculosis, PML).
  • History of brain tumor, stroke, severe head trauma or multiple sclerosis.
  • Active cancer, metabolic encephalopathy, severe cardiovascular or renal disease.
  • In the judgment of the PI, psychosis related to substance abuse or metabolic disorders.
  • Pregnancy or lactation.
  • Requirement for chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study.
  • History of or currently active primary or secondary immunodeficiency.
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
  • Contraindications to or intolerance of oral or IV corticosteroids.
What is involved?
  • Testing and Procedures: History, Clinical and Neurological Examination,  Psychological testing, questionnaires about your quality of life, ECGs (electrocardiograms), EEGs (Electroencephalograms – to check the electrical activity of the brain), blood and urine specimen collection, vital signs, and study drug administrations (total 2 intravenous infusions).
  • Frequency of visits:
      • Screening period – 1 to 2 visits (lasting about 2 hours)
      • Treatment and follow-up period – 8 visits (each one lasting about 4 hours)
  • Costs: No costs will be charged for any of the study procedures. To compensate the time and involvement, you will receive $350 once all the procedures requiring your participation have been completed.

 

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Active trials, but not currently enrolling participants


 

 

Donanemab in Early Symptomatic Alzheimer’s Disease

The purpose of this study is to see how safe and effective the study drug donanemab is in participants with early Alzheimer’s disease (AD). Donanemab is an antibody directed to target and remove deposited amyloid plaque, a key pathological hallmark of Alzheimer’s disease.

  • Study director (local PI): Joseph C. Masdeu, MD, PhD
  • Sponsor: Eli Lilly and Company
  • Recruiting?: No
  • Official study title: Assessment of Safety, Tolerability, and Efficacy of Donanemab in Early Symptomatic Alzheimer’s Disease (15T-MC-AACI) 
  • ClinicalTrials.gov identifier: NCT04437511
  • Conditions studied: Alzheimer’s Disease (AD)
  • Intervention Drugs: Donanemab (LY3002813) in comparison with placebo
  • Study Type: Interventional Study
  • Phase: Phase 3
  • Duration of participation: The expected time the subject will be in the study is around 18 months
  • IRB #: Pro00025839
  • IRB approval date: 9/8/2020

Eligibility
Inclusion criteria: 
Must meet all of the following clinical criteria for MCI due to AD or mild AD and must have:

  • Age: 60 Years to 85 Years
  • Gradual and progressive change in memory function reported by participants or informants for ≥ 6 months
  • An MMSE score between 20 and 28 (inclusive) at baseline
  • Meet florbetapir (amyloid) Positron Emission Tomography (PET) scan criteria
  • Meet flortaucipir PET scan criteria
  • Have enough communication and comprehension ability to consent to the performance of the study or have a legally authorized representative
  • Must have a reliable study partner who is in frequent contact with the participant (at least 10 hours per week) and will accompany the participant to study visits or be available by telephone at designated times

Exclusion criteria: 
All participants must not meet the following criteria:

  • Any significant neurological condition (other than Alzheimer's Disease) that might be a contributing cause of the subject's cognitive impairment
  • Advanced, severe progressive or unstable disease that may interfere with the safety, tolerability and study assessments, or put the participant at special risk.
  • Clinically significant unstable psychiatric illness, including history of schizophrenia or other psychosis
  • History of cancer within the last 5 years, except for non-metastatic skin cancer, non-progressive prostate cancer, or other cancers with low risk of recurrence as per the study doctor judgement.
  • History of unstable angina, myocardial infarction, advanced chronic heart failure, or clinically significant conduction abnormalities within 1 year prior to Screening
  • Indication of impaired renal or liver function
  • Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities
  • History of clinically significant multiple or severe drug allergies, or severe post-treatment hypersensitivity reactions
  • Any contraindications to brain magnetic resonance imaging (MRI) or PET scans
  • Alcohol or substance abuse in past 2 years
  • Are, in the judgement of the study doctor, actively suicidal and therefore deemed to be at significant risk for suicide

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
What is involved?

  • Testing and Procedures: History, vital signs, Clinical and Neurological Examination, Memory and Thinking Skills tests, Psychological testing, Brain MRIs, PET scans, ECGs, blood specimen collection (for biomarker and genetic testing), urine tests, and study drug / placebo infusions.
  • Frequency of visits:

There are about 32 planned clinic visits during the placebo controlled part of the study and up to 8 telephone safety follow-up contacts, as follows:

  • Screening Period – 7 weeks – 2 to 3 visits   
  • Treatment Period – 72 weeks – 18 visits  (once every 4 weeks when treatment will be administered).
  • Follow-up Period – 44 weeks – 4 visits contacts approximately 2 weeks after each of the first 8 doses.

The study doctor may ask you to attend for additional Unscheduled Visits for safety or before you start any new AD medication.

  • Costs: No costs will be charged for any of the study procedures. To compensate the time you take to undergo the procedures in this study, you will receive $50 - $300 (depending on the visit type and the study procedures involved in particular study visits) per completed study-related visit. You will also be reimbursed for costs related to your travel/ transportation, meals during study visits and hotel stay up to the limits set by the study sponsor. Your study partner will also receive $50 - $300 (depending on the visit type and the study procedures involved in particular study visits) per completed study-related visit. You and your study partner will be provided written details and the study team will discuss with both of you before you sign the consent.  You will receive the reimbursement in the form of a reloadable debit card provided by Greenphire company on behalf of the study sponsor.

 

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Alzheimer Prevention, A4, Study

The purpose of this study is to test whether an investigational drug called solanezumab can slow the progression of memory problems associated with brain amyloid (the protein that forms plaques in the brains of people with Alzheimer’s disease) as compared with placebo in subjects with preclinical AD.

  • Study director (local PI): Joseph C. Masdeu, MD, PhD
  • Sponsor: Eli Lilly & Company and National Institute on Aging (NIA)
  • Recruiting?: No
  • Official study title: Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4 Study)
  • ClinicalTrials.gov identifier: NCT02008357
  • Conditions studied: Risk for memory loss by amyloid brain deposition in older people
  • Intervention Drugs: Solanezumab and placebo control. Study drug (solanezumab or placebo) is administered as an intravenous infusion, every 4 weeks for 168 weeks.
  • Phase: Phase 3
  • Duration of participation: Up to 90 day screening period and 168 week treatment period
  • IRB #: Pro00013109
  • IRB approval date: 9/25/2015

Eligibility
Inclusion criteria: Subjects must be between 65–85 years of age (inclusive) and at screening have a Mini Mental State Examination (MMSE) score of 27–30 for subjects with high educational attainment (13 or more years of education) or 25–30 for subjects with low educational attainment (12 or fewer years of education). Subjects must have a Florbetapir PET scan at screening that shows evidence of brain amyloid pathology. Subjects must be on a stable dose of permitted medications for 6 weeks prior to the first infusion. Subjects must have a study partner who is willing to participate as a source of information and has at least weekly contact with the subject.
Exclusion criteria: Subjects must not be receiving acetylcholinesterase inhibitors (AChEI) and/or memantine at screening. Subjects must not lack good venous access. Subjects must not have any current serious or unstable illness including cardiovascular, hepatic, renal, respiratory, neurologic, psychiatric, or other conditions that could interfere with the study. Subjects must not have a history within the last 5 years of a serious infectious disease affecting the brain or head trauma resulting in loss of consciousness. Nor have history within the past 5 years of chronic alcohol or drug abuse or history within the past 2 years of major depression or bipolar disorder. Subjects must not have a history of schizophrenia or be at a serious risk for suicide.

What is involved?

  • Testing: Brain MRIs, Florbetapir PET scans, lumbar punctures (optional), neurological and physical examinations, cognitive testing and neuropsychiatric assessments, ECGs, blood, and urine specimen collection, vital signs
  • Frequency of visits:
      • Up to 90-day screening period
      • Visits once every 4 weeks for 168 weeks (“treatment period”)
      • Potential open-label treatment options following the treatment period
  • Materials needed prior to evaluation: No previous diagnosis of cognitive impairment
  • Costs: No costs will be charged for any of the study procedures. Parking will be validated for all study visits, and subjects will be reimbursed about $100 per visit.  

 

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Join a Research Study


 

Houston Alzheimer Disease Study (HADS)

The purpose of this study is to clarify at the individual level what genes and changes in the body predispose people to Alzheimer’s disease or other dementias. We will measure changes in brain imaging, body fluids, and memory or thinking abilities. Various types of brain imaging (Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET)) will tell us whether the patient have any of the abnormal proteins, amyloid and tau, that build up in the brain of people with Alzheimer’s disease. Body fluid samples (Blood and Cerebrospinal fluid (CSF)) will be extensively studied, to detect abnormalities that doctors are yet not aware of. We will measure the memory and other thinking abilities, which may be altered by the brain changes that occur in Alzheimer’s disease and similar diseases. We aim to provide data to set up a system to share the data we collect so that leading researchers working in this field can accelerate the discovery of new treatments.  

  • Study director (local PI): Joseph C. Masdeu, MD, PhD
  • Sponsor: Houston Methodist Research Institute
  • Recruiting?: Yes
  • Official study title: Houston Alzheimer Disease Study.
  • Conditions studied: Alzheimer’s Disease (AD), Mild Cognitive Impairment (MCI), and healthy volunteers.
  • Intervention Drugs: Drugs are not given in this study.
  • Study Type: Observational Study
  • Duration of participation: Natural history study with serial evaluations, with the periodicity required by clinical management and relevant research questions, usually no more than once yearly and generally less often. Study participants will be followed for several years, ideally five years or even longer. Note that this is an observational study and does not include receiving any medication to treat any disease, although participants can receive standard medications prescribed by their doctors and participate in any studies that evaluate potentially more effective medications.
  • IRB #: Pro00025999
  • IRB approval date: 8/11/2020

Eligibility
Inclusion criteria: 

  • Subjects must be 50 years of age or older.
  • Participant is not pregnant, lactating, or of childbearing potential
  • Must speak English or Spanish fluently.
  • Willing to undergo MRI and PET scans.
  • Have enough communication and comprehension ability to consent to the performance of the study or have a legally authorized representative.
  • Have a Study Partner (cognitively unimpaired participants may act as Study Partners for other cognitive unimpaired participants).
    • The study partner must be willing to attend study visits and participate as a source of information, including completing questionnaires about the memory and functioning of the participant.
    • The study partner must have weekly contact with the participant (contact can be in-person, via telephone or electronic communication).
    • Study participant must not have history of cognitive impairment.

Exclusion criteria: 
All participants must not meet the following criteria:

  • Inability to undergo MRI or PET scan for any reason, including severe claustrophobia.
  • History of large stroke or brain trauma, multiple sclerosis or other brain disorder that, in the judgement of the study doctor, may confound the study.
  • Pregnancy. In women in whom the possibility of pregnancy cannot be excluded, a pregnancy test must be performed on site the morning of any PET visit and a negative result together with a physician interview are required prior to the administration or any radiopharmaceutical.
  • Active cancer, metabolic encephalopathy, infection, cardiovascular disease.
  • Research or clinical radiation exposure greater than 50 mSv in the previous 12 months.
What is involved?
  • Testing and Procedures: History, Clinical and Neurological Examination,  Psychological testing, Brain MRIs, amyloid and tau PET scans, spinal tap (optional),  blood specimen collection, and vital signs
  • Frequency of visits: Participants will have serial evaluations, with the periodicity required by clinical management and relevant research questions, usually no more than once yearly and generally less often, but always within the NIH limits of research radiation exposure.
  • Costs: No costs will be charged for any of the study procedures. To compensate the time, you take to undergo the procedures in this study, you will receive $50 for each MRI study, $75 for each PET study. These amounts will be paid to you approximately one month after completing each procedure.



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ER 176 Inflammation PET in AD

The discovery of AD risk genes coding for proteins involved in inflammation has revived the interest in neuroinflammation (or brain inflammation) in the pathogenesis of AD. To understand the role of inflammation in the pathogenesis of AD, it is important to measure inflammation in the brain of people with AD and its relationship with abnormal forms of brain proteins (β-amyloid [Aβ]) and tau, as the disease progresses. So far, there is no in vivo data in humans verifying either a neuroprotective or harmful role of inflammation in the progression of AD. To clarify these issues, we will study inflammation in the brain of 100 patients with Alzheimer’s disease, 10 patients with old head trauma or frontotemporal dementia and 40 healthy volunteers by means of a PET tracer (11C-ER176).

  • Study director (local PI): Joseph C. Masdeu, MD, PhD
  • Sponsor: Houston Methodist Hospital Foundation.
  • Recruiting?: Yes
  • Official study title: Role of Brain Inflammation in Alzheimer’s Disease
  • Conditions studied: 
  • Alzheimer’s Disease (AD), Frontotemporal Dementia (FTD), Chronic Head Injury/Chronic Traumatic Encephalopathy (CTE) and healthy volunteers
  • Intervention Drugs: Drugs are not given in this study.
  • Study Type: Observational Study
  • Duration of participation: The expected time the subject will be in the study is between 4 to 6 weeks
  • IRB #: Pro00018693
  • IRB approval date: 3/6/2018

Eligibility
Inclusion criteria: 

  • Subjects must be between 40 years to 90 years (inclusive) of age.
  • Participant is not pregnant, lactating, or of childbearing potential
  • Must speak English or Spanish fluently.
  • Willing to undergo MRI and PET scans.

For ‘Healthy’ Volunteers:

  • Participant with or without subjective memory complaints, verified by a study partner, beyond what one would expect for age.
  • Have enough communication and comprehension ability to consent to the performance of the study.

For ‘FTD or CTE’ Patients

  • Participant must have a clinical diagnosis of CTE or FTD, such as non-amyloid logopenic primary progressive aphasia, progressive supranuclear palsy or corticobasal degeneration.

For "Alzheimer's Disease" Patients:

  • Participant must express a subjective memory concern as reported by participant or recalled by study partner or clinician.
  • Have sufficient communication and comprehension ability to consent to the performance of the study or have a legally authorized representative.

Exclusion criteria: 
All participants must not meet the following criteria:

  • Inability to undergo MRI or PET scan for any reason, including severe claustrophobia.
  • Pregnancy. In women in whom the possibility of pregnancy cannot be excluded, a pregnancy test must be performed on site the morning of any PET visit and a negative result together with a physician interview are required prior to the administration or any radiopharmaceutical.
  • Active cancer, metabolic encephalopathy, infection, cardiovascular disease.
  • Research or clinical radiation exposure greater than 40 mSv in the previous 12 months.

                 
For ‘Healthy’ Volunteers:

  • Any significant neurologic disease, such as Parkinson’s disease, multi-infarct dementia, Huntington’s disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.
  • Current primary Axis I or II psychiatric disorder.
  • Current use of psychotropic or anti-epileptic medication.
  • Substance abuse during the past two years.
  • Active hematological, renal, pulmonary, endocrine or hepatic disorders, except for treated thyroid disease.

For 'Alzheimer's Disease' Patients:

  • Any significant neurologic disease other than Alzheimer’s disease, such as Parkinson’s disease, multi-infarct dementia, Huntington’s disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, large stroke, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.

What is involved?

  • Testing and Procedures: History, Clinical and Neurological Examination,  Psychological testing, Brain MRI, Inflammation PET scan, arterial line placement,  ECGs, blood specimen collection, and vital signs
  • Frequency of visits:
      • Screening visit – 1
      • Clinical and Laboratory evaluation visit – 1
      • Imaging (MRI and PET scan) visit – 1  
  • Costs: No costs will be charged for any of the study procedures. To compensate the time, you take to undergo the procedures in this study, you will receive $50 for the MRI study, $150 for the PET study. These amounts will be paid to you approximately one month after completing each procedure.



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Tau and Inflammation PET in Alzheimer’s Disease

The discovery of AD risk genes coding for proteins involved in inflammation has revived the interest in neuroinflammation (or brain inflammation) in the pathogenesis of AD. To understand the role of inflammation in the pathogenesis of AD, it is important to measure inflammation in the brain of people with AD and its relationship with abnormal forms of brain proteins (β-amyloid [Aβ]) and tau, as the disease progresses. To measure inflammation and tau, we will obtain positron emission tomography (PET) scans after giving the person, in two different sessions, injections of [11C]ER176, and of [18F]MK6240 respectively. These investigational tracers will be taken up by the brain in proportion to the degree of inflammation and the amount of tau, which is increased in AD.

  • Study director (local PI): Joseph C. Masdeu, MD, PhD
  • Sponsor: Houston Methodist Research Institute
  • Recruiting?: Yes
  • Official study title: Tau and Brain Inflammation in Alzheimer’s Disease
  • Conditions studied: Alzheimer’s Disease (AD), Frontotemporal Dementia (FTD), Chronic Head Injury/Chronic Traumatic Encephalopathy (CTE) and healthy volunteers.
  • Intervention Drugs: Drugs are not given in this study.
  • Study Type: Observational Study
  • Duration of participation: The expected time the subject will be in the study is around 12 weeks
  • IRB #: Pro00020634
  • IRB approval date: 12/18/2018

Eligibility
Inclusion criteria: 

  • Individuals of either sex, 40-90 years of age .
  • Participant is not pregnant, lactating, or of childbearing potential
  • Must speak English or Spanish fluently.
  • Willing to undergo PET scans.

For ‘Healthy’ Volunteers:

  • Participant with or without subjective memory complaints, verified by a study partner, beyond what one would expect for age.
  • Have enough communication and comprehension ability to consent to the performance of the study.

For ‘FTD or CTE’ Patients

  • Participant must have a clinical diagnosis of CTE or FTD, such as non-amyloid logopenic primary progressive aphasia, progressive supranuclear palsy or corticobasal degeneration.

For "Alzheimer's Disease" Patients:

  • Participant must express a subjective memory concern as reported by participant or recalled by study partner or clinician.
  • Have sufficient communication and comprehension ability to consent to the performance of the study or have a legally authorized representative.

Exclusion criteria: 
All participants must not meet the following criteria:

  • Inability to undergo MRI or PET scan for any reason, including severe claustrophobia.
  • Pregnancy. In women in whom the possibility of pregnancy cannot be excluded, a pregnancy test must be performed on site the morning of any PET visit and a negative result together with a physician interview are required prior to the administration or any radiopharmaceutical.
  • Active cancer, metabolic encephalopathy, infection, cardiovascular disease.
  • Research or clinical radiation exposure greater than 40 mSv in the previous 12 months.

                 
For ‘Healthy’ Volunteers:

  • Brain disorder, other than idiopathic headache
  • Current primary Axis I or II psychiatric disorder.
  • Current use of psychotropic or anti-epileptic medication.
  • Substance abuse during the past two years.
  • Active hematological, renal, pulmonary, endocrine or hepatic disorders, except for treated thyroid disease.

For 'Alzheimer's Disease' Patients:

  • Any significant neurologic disease other than Alzheimer’s disease, such as Parkinson’s disease, multi-infarct dementia, Huntington’s disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, large stroke, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.

What is involved?

  • Testing and Procedures: History, Clinical and Neurological Examination,  Psychological testing,  Brain MRI scan,  tau and inflammation PET scans, arterial line placement  blood specimen collection (for genotyping), and vital signs
  • Frequency of visits:
      • Screening visit – 1
      • Clinical and Laboratory evaluation visit – 1
      • Imaging (MRI and PET scan) visits – 2  
  • Costs: No costs will be charged for any of the study procedures. To compensate the time, you take to undergo the procedures in this study, you will receive $50 for the MRI study, $100 for [18F]MK6240 PET study and $150 for [11C]ER176 PET study. These amounts will be paid to you approximately one month after completing each procedure.



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ARTFL LEFFTDS Longitudinal Frontotemporal Dementia Study (ALLFTD)

The ARTFL LEFFTDS Longitudinal Frontotemporal Dementia (ALLFTD) study aims to evaluate sporadic (s-) and familial (f-) frontotemporal lobar degeneration (FTLD) patients and asymptomatic family members of f-FTLD patients, characterizing the cohorts longitudinally and informing clinical trial design. The study has two arms: a "longitudinal arm" involving a comprehensive assessment of clinical, functional, imaging, and biofluid data collection annually, and a "biofluid-focused arm" involving limited clinical data to accompany biospecimen collection.

  • Study director (local PI): Maria-Belen Pascual, PhD
  • Sponsor: National Institute on Aging (NIA) and the National Institute of Neurological Disease and Stroke (NINDS) through Mayo Clinic.
  • Recruiting?: Yes
  • Official study title: ARTFL LEFFTDS Longitudinal Frontotemporal Dementia Study (ALLFTD)
  • ClinicalTrials.gov identifier:  NCT04363684
  • Conditions studied: Frontotemporal Dementia (FTD)
  • Intervention Drugs: Drugs are not given in this study.
  • Study Type: Observational Study
  • Duration of participation: The expected time the participants will be in the study is one day for the ‘biofluid focused arm’ participants and up to 5 years (or less) for ‘longitudinal arm’ participants.
  • IRB #: Pro000241583
  • IRB approval date: 04/29/20

Eligibility
Inclusion criteria: 
For ‘Longitudinal Arm’ Patients

  • Familial FTLD (f-FTLD) participants (either is acceptable):
    • members of families in whom at least one member has a known disease-associated mutation in one of the major genes that cause f-FTLD: MAPT, GRN, C9orf72 (or other rare genes)
    • an autosomal dominant family history of a FTLD syndrome (without a known gene) verified by medical record review or well-documented family history including family members with a medical history consistent with FTLD or a related disorder.
  • Sporadic FTLD (s-FTLD) participants:
    • Sporadic participants should be symptomatic with no known family history nor a genetic mutation indicating f-FTLD. All sporadic participants must have an FTLD syndrome as a referring diagnosis; those determined by ALLFTD clinicians to have non-FTLD diagnoses will be excluded from longitudinal visits, but their baseline visit will be included in comparative datasets. For inclusion in the longitudinal follow-up, participants should meet research criteria for one of the following FTLD syndromes:
  • Progressive Supranuclear Palsy (PSP)
  • Semantic variant Primary Progressive Aphasia (svPPA)
  • Nonfluent variant Primary Progressive Aphasia (nfvPPA)
  • Behavioral variant Frontotemporal dementia (bvFTD)
  • Frontotemporal Dementia with Amyotrophic Lateral Sclerosis (FTD/ALS)

For "Biofluid-Focused" Arm Patients:

  • Participants enrolled in the biofluid arm may be either f-FTLD or s-FTLD. All general inclusion criteria apply. Participants should meet research criteria (as specified above) for any FTLD syndrome or meet familial FTLD inclusion criteria. Because the biofluid arm participants do not undergo the same detailed clinical and functional assessments required for the longitudinal arm, participants may be included regardless of primary language.
  • Participants (for both longitudinal and biofluid focused arms) must have a reliable study partner.

Exclusion criteria: 
All participants must not meet the following criteria:

  • Known presence of a structural brain lesion (e.g. tumor, cortical infarct) that could reasonably explain symptoms in a symptomatic participant.
  • Known presence of an Alzheimer's disease-causing mutation in PSEN1, PSEN2 or APP; or biomarker evidence for Alzheimer's disease as a cause of the clinical syndrome.
  • A previous history of Korsakoff encephalopathy, severe alcohol dependence (within 5 years of onset of dementia), frequent alcohol or other substance intoxication, or other neurological disorder.
  • Evidence through history or laboratory testing of uncorrected B12 deficiency, hypothyroidism, renal failure, liver failure, respiratory failure requiring supplemental oxygen.
  • Inability to undergo MRI scan for any reason, including severe claustrophobia.
  • Active cancer, metabolic encephalopathy, infection, cardiovascular disease.

                 
What is involved?
Testing and Procedures: History, Neurological Examination,  Memory and thinking testing, Brain MRI, , spinal tap (optional), pregnancy testing (if applicable),  blood specimen collection, Genetic testing and counseling (optional), and psychiatric consultations (optional)

  • Frequency of visits:
      • ‘Longitudinal Arm’ participants will have annual visits  to the study site. These visits usually span 2-3 days and involve above-mentioned procedures.  This is a long-term study where participants in this study arm will be asked to participate on a yearly basis  ( up to 5 yearly visits  over the course of study) for as long as they wish to participate or until the study is complete.
      • ‘Biofluid focused Arm’ participants’ study participation will last about 1 day, but they may be asked to intermittently complete short surveys remotely for up to five years. During the one in-person visit at the study site, they will have a brief physical and neurological exam, blood specimen collection and an optional spinal tap.
  • Costs: No costs will be charged for any of the study procedures. 
    • Subjects participating in ‘Longitudinal arm’ will receive $50 for each completed visit. Additionally, they will receive $50 for each MRI scan and $200 if they participate in the optional lumbar puncture procedure. If needed, participants will be assisted with the costs of travelling to Houston Methodist up to an agreed dollar amount. Prior to making any travel arrangements, participants will discuss with the study site personnel to assure the amounts can be approved. In order to receive a reimbursement for transportation, hotel, meals and parking expenses, they must provide a copy of the original itemized receipts.
    • Subjects participating in ‘Biofluid arm’ will receive $25 after their initial visit. Additionally, they will receive $50 if they participate in the optional lumbar puncture procedure.

 

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Longitudinal Early-onset Alzheimer’s Disease Study (LEADS)

Alzheimer’s disease (AD) is classified as early onset (EOAD) or late onset (LOAD).  In the early age onset form symptoms are seen before the age of 65. 
The purpose of this study is to investigate the differences between EOAD, LOAD, and cognitively normal (CN) elderly to gain a better understanding of the causes and changes associated with cognitive decline among individuals who get the disease before the age of 65.

  • Study director (local PI): Joseph C. Masdeu, MD, PhD
  • Sponsor: This study is being conducted by Indiana University (IU) and is funded by grants from the National Institute on Aging (NIA)
  • Recruiting?: Yes
  • Official study title: Longitudinal Early-onset Alzheimer’s Disease (LEADS)
  • ClinicalTrials.gov identifier:  NCT03507257
  • Conditions studied: Early-onset Alzheimer’s Disease (EOAD) and Cognitively Normal (CN) participants.
  • Intervention Drugs: Drugs are not given in this study.
  • Study Type: Observational Study
  • Duration of participation: Cognitively impaired participants (participants with EOAD) will take part in the study for 24 months; CN participants will take part in the study for 12 months.
  • IRB #: Pro00019097
  • IRB approval date: 9/11/2018

People who can participate in this study (“Inclusion Criteria”)

For "Early-onset AD" Subjects
  • Subjects must be between 40 years to 64 years (inclusive) of age.
  • Have a study partner who has frequent contact with the participant
  • Participant is not pregnant, lactating. Women must be two years post-menopausal, be surgically sterile, or have a negative pregnancy test prior to each PET scan.
  • Must speak English fluently.
  • Willing to undergo repeated MRIs and at least two PET scans
  • Agrees to collection of blood for safety labs, genomic analysis and biomarker testing.
For "Cognitively Normal" Subjects
  • Subjects must be between 40 years to 64 years (inclusive) of age
  • Have a study partner who has frequent contact with the participant
  • Participant with or without subjective memory complaints, verified by a study partner, beyond what one would expect for age.
  • Mini-Mental State Exam score between 26 and 30 inclusive.
  • Participant is not pregnant, lactating. Women must be two years post-menopausal, be surgically sterile, or have a negative pregnancy test prior to each PET scan.
  • Must speak English fluently.
  • Willing to undergo repeated MRIs and at least two PET scans
  • Agrees to collection of blood for safety labs, genomic analysis and biomarker testing.

People who have any of the following CANNOT participate in this study: 

  • Any significant neurologic disease other than Alzheimer’s disease, such as Parkinson’s disease, multi-infarct dementia, Huntington’s disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.
  • Two or more first degree relatives with a history of early-onset dementia.
  • Contraindications to  MRI (Magnetic Resonance Imaging) (e.g., claustrophobia, pacemaker, artificial heart valve, select ear implants, selective stents, metal fragments or foreign objects in the eyes, ears, skin or body, etc.)
  • Any significant systemic illness or unstable medical condition, which could lead to difficulty complying with the protocol (at the discretion of the Principal Investigator)
  • Current history (in previous 12 months) of mania, bipolar disorder with or without psychosis.
  • Current history (in previous 6 months ) of moderate or severe substance abuse
  • Residing in a 24-hour care skilled nursing facility.
  • History of risk factors for torsades de pointes (a cardiac dysrhythmia associated with sudden death) or taking medications known to prolong the QT interval. A list of restricted medications will be provided.
  • Previous participation in a therapeutic trial targeting amyloid or tau
  • For optional lumbar procedure only: history of laboratory values suggesting the risk of abnormal bleeding (e.g. low platelet count, etc.)

What is involved?

  • Testing and Procedures: History, Clinical and Neurological Examination, Memory and Thinking Skills tests, Computer based Memory testing, Psychological testing, Brain MRIs, Amyloid PET scans, Tau PET scans, lumbar punctures (optional), electrocardiograms, blood specimen collection (for routine safety labs, biomarker and genetic testing), and vital signs
  • Frequency of visits:
      • Screening visit – 1*
      • Baseline visit – 1*
      • Annual visits
        • Cognitively Normal participants – 1 visit*
        • Alzheimer’s Disease participants – 2 visits*

* Procedures will be scheduled across multiple days.

  • Costs: No costs will be charged for any of the study procedures. To compensate the time you take to undergo the procedures in this study, you will receive $50 for each MRI study, $100 for each PET study and $100 for each lumbar puncture. These amounts will be paid to you approximately one month after completing each procedure.

 

 

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Alzheimer’s Disease Neuroimaging Initiative 3 (ADNI3)

Alzheimer's Disease Neuroimaging Initiative (ADNI) has been realized in informing the design of therapeutic trials in Alzheimer's disease (AD). ADNI3 will continue to discover, optimize, standardize, and validate clinical trial measures and biomarkers used in AD research. This study will determine and define those measures of cognition and function, including composite measures, and those biomarker measures, which capture longitudinal change to detect treatment effects in clinical trials. Longitudinal change of cerebral tau measured with positron emission tomography (PET) scan will be correlated and compared with other measures. ADNI3 will determine which clinical, cognitive, and biomarker measures best predict the decline of cognition in Cognitively Normal (CN), Mild Cognitively Impaired (MCI) and AD participants. In addition, will determine which biomarker changes correlate with cognitive decline. This study is also aiming to determine the effects of other known disease proteins found in AD brains and genes, as well as newly discovered genes, proteins, and analytes that provide useful information concerning the pathogenesis / diagnosis of AD.

  • Study director (local PI): Joseph C. Masdeu, MD, PhD
  • Sponsor: This study is being funded by grants from National Institute on Aging (NIA) and U.S. Department of Defense.
  • Recruiting?: Yes
  • Official study title: Alzheimer’s Disease Neuroimaging Initiative 3 (ADNI3).
  • ClinicalTrials.gov identifier:  NCT02854033
  • Conditions studied: Alzheimer’s Disease (AD), Mild Cognitively Impaired (MCI) and Cognitively Normal (CN) participants.
  • Intervention Drugs: Drugs are not given in this study.
  • Study Type: Observational Study
  • Duration of participation: The expected time the subject will be in the study is between 3 and 5 years, depending on which study group the participant fit in.
  • IRB #: Pro00016334
  • IRB approval date: 7/7/2018
Eligibility
Inclusion criteria: 
  • Subjects must be between 55 years to 90 years (inclusive) of age.
  • Have a study partner who has frequent contact with the participant.
  • Visual and auditory acuity adequate for neuropsychological testing.
  • Participant is not pregnant, lactating, or of childbearing potential.
  • Completed six grades of education or has a good work history (sufficient to exclude mental retardation).
  • Must speak English or Spanish fluently.
  • Willing to undergo repeated MRIs and at least two PET scans.
  • Agrees to collection of blood for genomic analysis, APOE testing, biomarker testing and bio-specimen banking.
  • Agrees to at least one lumbar puncture for the collection of CSF.
  • Agrees to share genomic data and biomarker samples.

For "Cognitively Normal" Subjects:

  • Participant with or without subjective memory complaints, verified by a study partner, beyond what one would expect for age.
  • Mini-Mental State Exam score between 24 and 30 inclusive.

For "MCI (Minimal Cognitive Impairment) Adults":

  • Participant must express a subjective memory concern as reported by participant, or recalled by study partner or clinician.
  • Mini-Mental State Exam score between 24 and 30 inclusive (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director).
  • General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer’s disease cannot be made by the site physician at the time of the Screening Visit.

For "Alzheimer's Disease" Patients:

  • Participant must express a subjective memory concern as reported by participant, or recalled by study partner or clinician.
  • Mini-Mental State Exam score between 20 and 24 inclusive.

Exclusion Criteria: 
All participants must not meet the following criteria:
For 'Cognitively Normal' Subjects and for MCI Subjects:

  • Any significant neurologic disease, such as Parkinson’s disease, multi-infarct dementia, Huntington’s disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.

For 'Alzheimer's Disease' Patients:

  • Any significant neurologic disease other than Alzheimer’s disease, such as Parkinson’s disease, multi-infarct dementia, Huntington’s disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.

The following additional exclusion criteria apply to all diagnostic categories:
Exclusion Criteria Specific to AV-1451 PET:
The following criteria are exclusionary only for the AV-1451 scanning portion of the study:

  • History of risk factors for torsades de pointes (a cardiac dysrhythmia associated with sudden death) or taking medications known to prolong the QT interval. A list of restricted medications will be provided.
  • Have an ECG obtained prior to the AV-1451 PET scan that in the opinion of the investigator is clinically significant with regard to the subject’s participation in the study. Bazett’s corrected QT (QTcB) interval must be evaluated and must not exceed 458 msec in males, or 474 msec in females.
What is involved?
  • Testing and Procedures: History, Clinical and Neurological Examination, Memory and Thinking Skills tests, Computer based Memory testing, Psychological testing, Brain MRIs, Amyloid PET scans, Tau PET scans, FDG PET scans, lumbar punctures, ECGs, blood specimen collection (for biomarker and genetic testing), and vital signs.
  • Frequency of visits:
    • Screening visit – 1
    • Baseline visit – 1
    • Annual visits
      • Cognitively Normal participants – 4 visits
      • Mild Cognitively Impaired participants – 4 visits
      • Alzheimer’s Disease participants – 2 visits
  • Costs: No costs will be charged for any of the study procedures. To compensate the time you take to undergo the procedures in this study, you will receive $50 for each MRI study, $150 for each PET study and $190 for each lumbar puncture. These amounts will be paid to you approximately one month after completing each procedure.

 

 

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Inflammation in mTBI-PBR28

Persons who have suffered mild traumatic brain injury (mTBI) may experience cognitive problems and difficulties in interpersonal relationships. Some of these difficulties are caused by the brain disease itself, but doctors still do not understand well why this happens and therefore are limited in their ability to treat this problem.
Recent studies indicate that these problems could be associated brain inflammation. In order to clarify this issue, we plan to study brain inflammation in people with mTBI and healthy controls by means of a positron emission tomography (PET) scan, after the intravenous injection of a radioactive substance called [11C]PBR28. This study is likely to shed some light into why mTBI may cause problems with interpersonal relationships and cognition.

  • Study director: Joseph C. Masdeu, MD, PhD
  • Sponsor:  Houston Methodist Hospital Foundation
  • Recruiting?: No
  • Official study title: [11C]PBR28 PET to study microglial activation following mTBI
  • Conditions studied: Mild traumatic brain injury
  • Intervention Drugs: N/A.
  • Duration of participation: You will be expected to be in the study for about thirteen months, on which period of time, you may have up to 5 visits.
  • IRB #: Pro00014287
  • IRB approval date: 8/3/2016

Eligibility
Inclusion criteria:
Inclusion Criteria for mTBI Subjects

  • Individuals of either sex, 18-40 years of age
  • Have sustained within the previous week an alteration in brain function caused by a process of sudden acceleration/deceleration of the brain. The alteration of brain function is defined by having one or more of the following clinical signs:
    • Any period of loss of or a decreased level of consciousness (LOC)
    • Any loss of memory for events immediately before (retrograde amnesia) or after the injury (Post-Traumatic Amnesia, PTA)
    • Neurologic deficits (weakness, loss of balance, change in vision, dyspraxia paresis/plegia [paralysis], sensory loss, aphasia, etc.)
    • Any alteration in mental state at the time of the injury (confusion, disorientation, slowed thinking, etc.) not due to intoxication, medications, or multiple trauma to other body regions
  • Fluent in English and have sufficient communication and comprehension ability to consent to the performance of the study
  • With a TSPO genotype that allows at least partial binding of [11C]PBR28

Inclusion Criteria for Healthy Volunteers

  • Individuals of either sex, 18-40 years of age
  • Fluent in English and have enough communication and comprehension ability to consent to the performance of the study
  • With a TSPO genotype that allows at least partial binding of [11C]PBR28

Inclusion Criteria for Controls with Chronic Traumatic Encephalopathy, Alzheimer’s disease, or Frontotemporal Dementia

  • Individuals of either sex, 30-90 years of age with the clinical diagnosis of CTE, AD, PSP or FTD
  • Fluent in English and have enough communication and comprehension ability to consent to the performance of the study
  • With a TSPO genotype that allows at least partial binding of [11C]PBR28

Exclusion criteria: 
Exclusion Criteria for mTBI Subjects

  • Inability to undergo MRI or PET for any reason, including severe claustrophobia
  • Being treated with steroids or large doses of other anti-inflammatory drugs
  • Loss of consciousness longer than 30 min in connection with the traumatic event
  • Post-traumatic amnesia lasting more than 24 hours after mTBI
  • Glasgow Coma Scale score lower than 13 after the mTBI
  • History of previous moderate to severe TBI
  • Brain disorder, other than idiopathic headache, prior to mTBI
  • Current primary Axis I or II psychiatric disorder
  • Current use of psychotropic or anti-epileptic medication
  • Substance abuse during the past two years
  • Active cancer, metabolic encephalopathy, infection, cardiovascular disease
  • Active hematological, renal, pulmonary, endocrine or hepatic disorders, except for treated thyroid disease
  • Pregnancy

Exclusion Criteria for Healthy Volunteers

  • Inability to undergo MRI or PET for any reason, including severe claustrophobia
  • Being treated with steroids or large doses of other anti-inflammatory drugs
  • History of previous TBI of any kind
  • Brain disorder, other than idiopathic headache
  • Current primary Axis I or II psychiatric disorder
  • Current use of psychotropic or anti-epileptic medication
  • Substance abuse during the past two years
  • Active cancer, metabolic encephalopathy, infection, cardiovascular disease
  • Active hematological, renal, pulmonary, endocrine or hepatic disorders, except for treated thyroid disease
  • Pregnancy

Exclusion Criteria for Controls with Chronic Traumatic Encephalopathy, Alzheimer’s disease, or Frontotemporal Dementia

  • Inability to undergo MRI or PET for any reason, including severe claustrophobia
  • Active cancer, metabolic encephalopathy, infection, severe cardiovascular disease
  • Being treated with steroids or large doses of other anti-inflammatory drugs, at the judgment of the PI
  • Pregnancy

What is involved?

  • Testing: History, Behavior, Blood specimen collection for genotyping, Neurological and neuropsychological examinations, Brain MRIs, PBR28  PET scans.
  • Frequency of visits: Usually 4 visits, but may have up to 5 visits.
  • Costs: The study will cover the cost of the clinical and neuropsychological examinations, the PET scan, and the MRI study. You will receive $100 per completed visit to help pay for parking and to compensate for your time.

 

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Neuroimaging in Cognitive Disorders

The purpose of this study is to evaluate the usefulness in cognitive disorders of several different tests, including various types of brain imaging, body fluid samples, measurements of memory and other thinking abilities, and measures of functional independence. We aim to identify the best imaging measures or other markers in the blood, urine, and cerebrospinal fluid for diagnosing AD and related disorders and for tracking changes over time. It is important to improve our ability to measure changes in AD and related disorders over time because these measures may help us advise patients and families about the rate of progression of the disease and will be very important for making decisions about whether new treatments work.

  • Study director: Joseph C. Masdeu, MD, PhD
  • Sponsor: Nantz National Alzheimer Center, Houston Methodist Neurological Institute
  • Recruiting?: Yes
  • Official study title: Neuroimaging in Alzheimer Disease and related disorders
  • Conditions studied: Alzheimer’s disease; Healthy volunteers are also enrolled
  • Intervention Drugs: N/A.
  • Phase: Observational study
  • Duration of participation: Natural history study with serial evaluations, with the periodicity required by clinical management and relevant research questions, usually no more than once yearly and generally less often.
  • IRB #: Pro00007462
  • IRB approval date: 2/28/2013

Inclusion criteria: 
All enrolled subjects will be between 18 and 90 (inclusive) years of age and have a diagnosis of Alzheimer disease or a related disorder or a strong family history or other genetic risk factors for those diseases. They must be native in English or Spanish and willing to undergo MRI and PET scanning. All subjects must be willing and able to undergo all testing procedures, including neuroimaging and lumbar puncture, and agree to longitudinal follow-up.

Exclusion criteria: 
Include significant or unstable medical illness (e.g., poorly controlled diabetes, active cancer), clinically significant laboratory abnormalities on screening tests (e.g., thyroid function), contraindication to MRI including pacemaker, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body, the use of warfarin or presence of blood conditions that are a contraindication to lumbar puncture, and any contraindications to PET scanning, such as having reached the annual radiation dose prescribed by radiation safety guidelines.

What is involved?
Testing: Each evaluation may include clinical and neuropsychological examinations, a MRI scan, an 18F-Fluorodeoxyglucose PET scan, PIB PET scan or an 18F-florbetapir PET scan. In addition, blood (not to exceed 40 ml in each extraction) and urine will be collected and a lumbar puncture (optional) will be obtained for measurement of dementia-related biomarkers. 

  • Frequency of visits: Participants will have serial evaluations, with the periodicity required by clinical management and relevant research questions, usually no more than once yearly and generally less often, but always within the NIH limits of research radiation exposure.
  • Costs: You will only receive a small incentive amount for tests that involve some physical hardship, namely, $100 for a spinal tap. Parking passes will be validated.


 

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NMDA Receptor Antibodies in Psychosis

Schizophrenic and bipolar psychoses are chronic and disabling brain disorders that affect people of all backgrounds. It is thought that in the brain of people with schizophrenic psychosis there is a decreased amount of a receptor known as the N-acetyl methyl D-aspartate (NMDA) receptor, which normally facilitates thinking and memory. It is not known why this receptor is decreased, but a reasonable possibility is that in some people the receptor is being attacked by antibodies, produced by the body of the person with psychosis.

The goal of this study is to determine whether there are increased antibodies against the NMDA receptor in cerebrospinal fluid (CSF) and serum of people with psychosis, when compared with healthy controls. Recognizing this problem is critical because when the antibodies are lowered by treatment, the NMDA receptors recover, and the psychosis would be eliminated or at least greatly improved.

  • Study director: Joseph C. Masdeu, MD, PhD
  • Sponsor:  The Schizophrenia Collaborative Fund
  • Recruiting?: Yes
  • Official study title: NMDA Receptor in Psychosis: Specific Auto-Antibodies
  • Conditions studied: Psychosis
  • Intervention Drugs: N/A.
  • Phase: Observational study
  • Duration of participation: The expected time you will be in the study is about 1 month.
  • IRB #: Pro00014773
  • IRB approval date: 9/30/2016

Inclusion criteria: 
Inclusion Criteria for Psychosis Subjects:

  • Individuals of either sex, 18-35 years of age
  • Admitted for a psychotic episode in its broadest definition, including manic psychosis
  • Normal academic performance at least until the age of 15 years and absence of psychiatric symptoms before the same age
  • Have sufficient communication and comprehension ability to assent or consent to the performance of the study. Both English and Spanish speaking subjects will be included

Inclusion Criteria for Healthy Volunteers:

  • Individuals of either sex, 18-35 years of age
  • Have enough communication and comprehension ability to consent to the performance of the study. Both English and Spanish speaking subjects will be included

Exclusion criteria: 
Exclusion Criteria for Psychosis Subjects

  • History of brain tumor, stroke, epilepsy, severe head trauma or multiple sclerosis
  • In the judgment of the PI, psychosis related to substance abuse or metabolic disorders
  • Active cancer, metabolic encephalopathy, infection, severe cardiovascular or renal disease
  • Current antiplatelet or anticoagulation medication

Exclusion Criteria for Healthy Volunteers

  • History of brain tumor, stroke, severe head trauma or multiple sclerosis
  • Primary Axis I or II psychiatric disorder
  • Current use of psychotropic or anti-epileptic medication
  • Active cancer, metabolic encephalopathy, infection, cardiovascular disease
  • Active hematological, renal, pulmonary, endocrine or hepatic disorders
  • Current antiplatelet or anticoagulation medication

What is involved?

  • Testing:  Lumbar punctures, neurological and physical examinations, cognitive testing and neuropsychiatric assessments, blood specimen collection.
  • Materials needed prior to evaluation: Reports of EEGs and imaging procedures, such as brain CT or MRI (those that were done previously as a part of a standard of care), but removing from the information that could be traced them back to you.
  •  Costs: No costs will be charged for any of the study procedures. To compensate your time in the study, you will receive $150.00 once you have completed all the procedures of the study.

 

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Social Cognition and Neuroimaging in FTD

People with some diseases that affect the brain, such as Alzheimer’s disease or fronto-temporal dementia, may experience difficulties in interpersonal relationships. Some of these difficulties are caused by the brain disease itself, but doctors still do not understand well why this happens and therefore are limited in their ability to treat this problem.
In order to clarify this issue, we plan to study the response of people with Alzheimer’s disease or fronto-temporal dementia to interpersonal relationship situations. We will also study their brain by means of magnetic resonance imaging (MRI) and positron emission tomography (PET). This study is likely to shed some light into why these diseases may cause problems with interpersonal relationships.

  • Study director: Joseph C. Masdeu, MD, PhD and Maria Belen Pascual, PhD
  • Sponsor: Nantz National Alzheimer Center, Houston Methodist Neurological Institute
  • Recruiting?: Yes
  • Official study title: Neuroimaging Correlates of Social Cognition in Frontotemporal Dementia
  • Conditions studied: Frontotemporal dementia, Alzheimer’s disease; healthy volunteers are also included
  • Intervention Drugs: N/A.
  • Phase: Observational study.
  • Duration of participation: 3 year
  • IRB #: Pro00011837
  • IRB approval date:1/30/2015

Eligibility
Inclusion criteria: 

  • Patients: All enrolled patients will be between 30 and 90 (inclusive) years of age and have a diagnosis of FTD or AD. They must be fluent in English or Spanish and willing to undergo MRI 3 Tesla neuroimaging and PET scanning. All subjects must be willing and able to undergo all testing procedures, including MRI and PET.
  • Healthy volunteers:  All enrolled healthy volunteers will be between 30 and 90 (inclusive) years of age and cognitively intact. They must be fluent in English or Spanish and willing to undergo MRI 3 Tesla neuroimaging scanning. All subjects must be willing and able to undergo all testing procedures, including MRI.

Exclusion criteria: 

  • Include significant or unstable medical illness (e.g., poorly controlled diabetes, active cancer), clinically significant laboratory abnormalities on screening tests (e.g., thyroid function), contraindication to MRI including pacemaker, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body, and any contraindications to PET scanning, such as having reached the annual radiation dose prescribed by radiation safety guidelines and pregnancy.

What is involved?

  • Testing: Brain MRI, PIB PET scan, and for some (around 20) participants, two other optional PET scans (AV-1451 and PBR28) may be asked; arterial line placement, neurological and physical examinations, cognitive testing and neuropsychiatric assessments, and blood specimen collection.
  • Frequency of visits: 4 visits (We will use around 13 hours of your time in the entire study)
  • Materials needed prior to evaluation: We will ask you to have a study partner who is willing to take part with you in this study. Your study partner is someone who knows you well and is willing to answer a 10-minute questionnaire, either in person or over the telephone, about your daily living skills.
  • Costs: No costs will be charged for any of the study procedures. Parking will be validated for all study visits. 

For more information, please contact clinical research coordinator Victoria Arbones, RN, at varbones@houstonmethodist.org or call 713.441.7650. 

 

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Spinal Cord Inflammation in ALS

Amyotrophic lateral sclerosis (ALS) is currently an incurable disease with an average lifespan after diagnosis of about 6 years. People with ALS get worse in part because there is inflammation in the spinal cord. However, only now we have a procedure that could possibly allow doctors to measure inflammation in the spinal cord. This procedure is called a [11C]PBR28 positron emission tomography (PET) scan.
This study will allow us to determine whether or not this procedure can be used to measure inflammation in the spinal cord and compare it with the inflammation in the brain, measured also with PET. Measuring inflammation is very important as it will allow doctors to determine whether medications they are giving to reduce inflammation in ALS are working or not.

  • Study director: Joseph C. Masdeu, MD, PhD
  • Sponsor: Houston Methodist Hospital Foundation
  • Recruiting?: Yes
  • Official study title: [11C]PBR28 PET to study microglial activation in amyotrophic lateral sclerosis spinal cord
  • Conditions studied: Amyotrophic lateral sclerosis; however, patients with Multiple Sclerosis and healthy volunteers will also be enrolled as control subjects.
  • Intervention Drugs: N/A.
  • Phase: Observational study
  • Duration of participation: The expected time you will be in this study is around 2 months.
  • IRB #: Pro00014287
  • IRB approval date: 4/1/2016

Eligibility
Inclusion criteria: 
Inclusion Criteria for ALS Subjects

  • Individuals of either sex, 18-75 years of age
  • Have sporadic or familial ALS
  • Have sufficient communication and comprehension ability to consent to the performance of the study
  • With a TSPO SNP genotype that allows at least partial binding of [11C]PBR28

Inclusion Criteria for Healthy Volunteers

  • Individuals of either sex, 18-75 years of age
  • Have enough communication and comprehension ability to consent to the performance of the study
  • With a TSPO SNP genotype that allows at least partial binding of [11C]PBR28

Inclusion Criteria for Controls with Multiple Sclerosis

  • Individuals of either sex, 18-75 years of age with the clinical or imaging diagnosis of spinal inflammatory lesions
  • Have enough communication and comprehension ability to consent to the performance of the study
  • With a TSPO SNP genotype that allows at least partial binding of [11C]PBR28

Exclusion criteria: 

Exclusion Criteria for ALS Subjects

  • Inability to undergo MRI or PET for any reason, including:
    • History of a cardiac pacemaker or pacemaker wires
    • Metallic particles in the body
    • Prosthetic heart valves
    • Claustrophobia
  • Being treated with steroids or large doses of other anti-inflammatory drugs
  • Presence of diaphragm pacing system (DPS)
  • The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the subject to provide informed consent
  • Active cancer, metabolic encephalopathy, infection, cardiovascular disease
  • Active hematological, renal, pulmonary, endocrine or hepatic disorders, except for treated thyroid disease
  • Pregnancy or current breastfeeding

Exclusion Criteria for Healthy Volunteers

  • Inability to undergo MRI or PET for any reason, including severe claustrophobia
  • Being treated with steroids or large doses of other anti-inflammatory drugs
  • Substance abuse during the past two years
  • Active cancer, metabolic encephalopathy, infection, cardiovascular disease
  • Active hematological, renal, pulmonary, endocrine or hepatic disorders, except for treated thyroid disease
  • Pregnancy

Exclusion Criteria for Controls with Multiple Sclerosis

  • Inability to undergo MRI or PET for any reason, including severe claustrophobia
  • Active cancer, metabolic encephalopathy, infection, severe cardiovascular disease
  • Being treated with steroids or large doses of other anti-inflammatory drugs
  • Pregnancy

What is involved?

  • Testing: Spinal cord MRI and PBR PET scans, arterial line placement, EMGs, neurological and physical examinations including motor strength testing, blood specimen collection.
  • Frequency of visits: 4 visits
  • Costs: No costs will be charged for any of the study procedures. You will be compensated $100 for the PET scan and $100 for the MRI scan.  This will help pay for your time and any incidentals like parking and food.


 

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Tau imaging in acute mTBI

Persons who have suffered mild traumatic brain injury (mTBI) may experience cognitive problems and difficulties in interpersonal relationships. Some of these difficulties are caused by the brain disease itself, but doctors still do not understand well why this happens and therefore are limited in their ability to treat this problem.
Recent studies indicate that these problems could be associated with the deposition in the brain of an abnormal form of a protein called tau. In order to clarify this issue, we plan to study the brain accumulation of this protein in people with mTBI by means of a positron emission tomography (PET) scan, after the intravenous injection of a radioactive substance called AV1451.

  • Study director: Joseph C. Masdeu, MD, PhD
  • Sponsor:  Houston Methodist Hospital
  • Recruiting?: Yes
  • Official study title: [18F]AV-145 PET to study ptau in vivo in the evolution of acute mTBI
  • Conditions studied: Mild traumatic brain injury (Concussion)
  • Intervention Drugs: N/A.
  • Phase: Observational study
  • Duration of participation: You will be expected to be in the study for about thirteen months, but will only have to come for 2, or, optionally, 3 visits.
  • IRB #: Pro00012451
  • IRB approval date: 4/13/2015

Eligibility
Inclusion criteria:
mTBI Patients

  • Individuals of either sex, 18-40 years of age.
  • Have sustained within the previous week an alteration in brain function caused by a process of sudden acceleration/deceleration of the brain.
  • The alteration of brain function is defined by having one or more of the following clinical signs:
  • Any period of loss of or a decreased level of consciousness (LOC)
  • Any loss of memory for events immediately before (retrograde amnesia) or after the injury (Post-Traumatic Amnesia, PTA)
  • Neurologic deficits (weakness, loss of balance, change in vision, dyspraxia paresis/plegia [paralysis], sensory loss, aphasia, etc.)
  • Any alteration in mental state at the time of the injury (confusion, disorientation, slowed thinking, etc.) not due to intoxication, medications, or multiple trauma to other body regions.
  • Fluent in English and have sufficient communication and comprehension ability to consent to the performance of the study.

Healthy volunteers

  • Individuals of either sex, 18-85 years of age.
  • Fluent in English and have enough communication and comprehension ability to consent to the performance of the study.

Patients with CTE , AD or FTD

  • Individuals of either sex, 30-85 years of age with the clinical diagnosis of CTE, AD, or FTD.
  • Fluent in English and have enough communication and comprehension ability to consent to the performance of the study.

Exclusion criteria: 
mTBI patients

  • Inability to undergo MRI or PET for any reason, including severe claustrophobia.
  • Medications that interfere with the performance of [18F]AV-1451 PET.
  • Loss of consciousness longer than 30 min in connection with the traumatic event.
  • Post-traumatic amnesia lasting more than 24 hours after mTBI.
  • Glasgow Coma Scale scores lower than 13 after the mTBI.
  • History of previous moderate to severe TBI.
  • Brain disorder, other than an idiopathic headache, prior to mTBI.
  • Current primary Axis I or II psychiatric disorder.
  • Current use of psychotropic or anti-epileptic medication.
  • Substance abuse during the past two years.
  • Active cancer, metabolic encephalopathy, infection, cardiovascular disease.
  • Active hematological, renal, pulmonary, endocrine or hepatic disorders, except for treated thyroid disease.
  • Pregnancy.

Healthy volunteers

  • Inability to undergo MRI or PET for any reason, including severe claustrophobia.
  • Medications that interfere with the performance of [18F]AV-1451 PET.
  • History of previous TBI of any kind.
  • Brain disorder, other than an idiopathic headache.
  • Current primary Axis I or II psychiatric disorder.
  • Current use of psychotropic or anti-epileptic medication.
  • Substance abuse during the past two years.
  • Active cancer, metabolic encephalopathy, infection, cardiovascular disease.
  • Active hematological, renal, pulmonary, endocrine or hepatic disorders, except for treated thyroid disease.
  • Pregnancy.

Patients with CTE CTE, AD or FTD

  • Inability to undergo MRI or PET for any reason, including severe claustrophobia.
  • Active cancer, metabolic encephalopathy, infection, severe cardiovascular disease.
  • Pregnancy

What is involved?

  • Testing: History, Behavior, Neurological and neuropsychological examinations, an AV1451  PET scan.
  • Frequency of visits: Mainly 2 visits, and an optional 3rd visit.
  • Costs: The study will cover the cost of the clinical and neuropsychological examinations, as well as the PET scan. You will be paid $300 for taking part in the study. Parking passes will be validated.

 

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Completed Studies

  1. Anti-tau Antibody in Mild Cognitive Impairment and Alzheimer’s disease – Tango Study
  2. Chronic severe TBI: tau and inflammation PET
  3. Hand Control in Alzheimer's Disease
  4. Inflammation in mTBI-PBR28
  5. Tau imaging in acute mTBI
  6. Anti-tau Antibody in Early Alzheimer’s (AbbVie) – Extension Study
  7. Aducanumab in Early Alzheimer’s Disease.
  8. An Efficacy and Safety Study of JNJ-54861911 in Participants Who Are Asymptomatic at Risk for Developing Alzheimer's Dementia -
  9. A Study of CAD106 and CNP520 versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease 
  10. BACE-inhibitor to Decrease Beta-amyloid in Mild Alzheimer's (Lilly) 
  11. Antibody and BACE Inhibitor in Alzheimer’s
  12. AV1451 Pathology Validation Study 
  13. Blood markers of mTBI
  14. TRACK-ALS-001
  15. Anti-tau Antibody in Early Alzheimer’s (AbbVie)
  16. Tau Antibody in Early Alzheimer’s Disease (Lilly) – Periscope
  17. Treatment of Agitation in Alzheimer’s disease
  18. Pimavanserin in Dementia-related Psychosis

 

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