- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05063851
The Use of Memantine for Prevention of Alzheimer's Disease
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The use of memantine for prevention of Alzheimer's Disease (AD) is designed to assess the feasibility of the use of memantine hydrochloride for prevention of AD and provide design elements for a Phase 3 efficacy study.
Up to 128 subjects will be enrolled/screened to achieve a sample size of 32 randomized participants with a 1:1 randomization allocation. The study population will include individuals, 50-65 years of age, who are APOE4 positive with a family history of Alzheimer's Disease who meet all other eligibility criteria.
The schedule of assessments includes screening/baseline, treatment period (including titration up/down) and follow up/end of study over 101 weeks for each subject. Study efficacy assessments are the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Montreal Cognitive Assessment (MoCA), Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL), Cognitive Function Index, Alzheimer's Disease Cooperative Study - Activities of Daily Living Prevention Instrument Activities of Daily Living - Prevention Instrument and the Clinical Dementia Rating Scale (CDR) Scale. Safety assessments include the Center for Epidemiologic Studies Depression Scale (CES-D) Vital Signs, Physical/Neurological Exam, Electrocardiogram, Blood Chemistries, Urinalysis, Medical History, Assessment of Adverse Events and Concomitant Medications, MRI and PET imaging.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Amy Fansler
- Phone Number: 434-243-1760
- Email: acf7h@virginia.edu
Study Locations
-
-
Virginia
-
Charlottesville, Virginia, United States, 22908
- Recruiting
- University of Virginia
-
Contact:
- Kimberlee Meegan
- Phone Number: 434-243-2040
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Principal Investigator:
- Carol Manning, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Be between the age of 50 and 65 years at time of informed consent.
- Have a positive family history for dementia (minimum of 1 first degree relative).
- Previously known or documented heterozygote or homozygote ApoE ε4 allele.
- Be able to read and write and must have adequate hearing and visual acuity to complete the psychometric tests.
- Be otherwise healthy for their age group or medically stable with or without medication on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening or at baseline.
- Have Montreal Cognitive Assessment (MOCA) score of 27 or above.
- Have a creatinine clearance (CrCl), estimated using the Cockcroft-Gault formula, greater or equal to 30 mL/minute.
Exclusion Criteria:
- A current clinical condition or requires a medication that raises the pH of their urine.
- Severe renal or hepatic impairment.
- Any other abnormality that could cause a possible cognitive deficit (including, but not limited to, vascular encephalopathy or large strokes).
- Contraindications for MRI (e.g., prostheses, implants, claustrophobia, pacemaker) or PET imaging.
- Neurodegenerative disorder known to cause neurocognitive decline
- Relevant history of or current neurological disease other than preclinical AD, which may make interpretation of possible new neurological signs or symptoms difficult.
- Clinically significant and active pulmonary, gastrointestinal, renal, hepatic, endocrine, or cardiovascular system disease
- Ongoing cancer treatment
- Clinically significant and active psychiatric disorder
- Use of an investigational medical device within 3 months before the planned start of study.
- Current participation in an interventional study with an investigational drug component.
- Major surgery (e.g., requiring general anesthesia) within 8 weeks before screening, or will not have fully recovered from surgery, or has major surgery planned during the time the subject is expected to participate in the study.
- Requires treatment with an AChE inhibitor or any of the following: acetazolamide, methazolamide, amantadine, ketamine, dextromethorphan.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
|
The recommended starting dose of memantine hydrochloride/placebo is 5 mg once daily.
The dose should be increased in 5 mg increments to 10 mg/day (5 mg twice daily), 15 mg/day (5 mg and 10 mg as separate doses), and 20 mg/day (10 mg twice daily).
The minimum recommended interval between dose increases is one week.
The dosage shown to be effective in controlled clinical trials is 20 mg/day.
|
Experimental: Memantine hydrochloride
|
The recommended starting dose of memantine hydrochloride/placebo is 5 mg once daily.
The dose should be increased in 5 mg increments to 10 mg/day (5 mg twice daily), 15 mg/day (5 mg and 10 mg as separate doses), and 20 mg/day (10 mg twice daily).
The minimum recommended interval between dose increases is one week.
The dosage shown to be effective in controlled clinical trials is 20 mg/day.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To assess the feasibility of the use of memantine hydrochloride for prevention of Alzheimer's Disease as measured by the percentage of patients who are lost to follow-up
Time Frame: Baseline to 24 months
|
The percentage of subjects who are lost to follow-up before completion of the protocol will be calculated, along with 95% confidence intervals.
Calculations will be carried out in the entire randomized population, and by treatment arm.
Loss to follow-up percentages will be compared between arms using Fisher's exact tests.
Permutation tests will be used to assess if any baseline subject characteristics are associated with overall loss to follow-up percentages, or time to loss to follow-up.
|
Baseline to 24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Summary of demographic characteristics of subjects overall, and in each arm.
Time Frame: Baseline to 24 months
|
Permutation tests, Fisher's exact tests, or Mann-Whitney U-tests will be used depending on the data distributions observed.
This is a needed design estimate for a Phase 3 efficacy trial.
|
Baseline to 24 months
|
Mean change in RBANS scores from baseline to end of protocol, overall and in each arm.
Time Frame: Baseline to 24 months
|
The changes from baseline to 24 months will be calculated for each individual who completes the study.
Both absolute and relative changes will be computed for each measurement.
T-tests or Mann-Whitney U-test will be used to compare the change scores between arms.
Additionally, since measurements are also planned at 12 months, an analysis will be performed using all available data on each subject.
This analysis will use a random effects model to estimate the trajectories of change over time in each arm.
The random effects model will also be used to assess the potential effect of each demographic variable on the change in RBANS.
This is a needed design estimate for a Phase 3 efficacy trial.
|
Baseline to 24 months
|
Intraclass correlation coefficient (ICC) for longitudinal follow-up
Time Frame: Baseline to 24 months
|
The ICC will be calculated by dividing the random effects variance in the random effects model (above) by the total variance.
This is a needed design estimate for a Phase 3 efficacy trial.
|
Baseline to 24 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Carol Manning, PhD, Professor of Neurology
- Principal Investigator: Anelyssa D'Abreu, MD, Associate Professor of Neurology
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Neurodegenerative Diseases
- Dementia
- Tauopathies
- Alzheimer Disease
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Dopamine Agents
- Antiparkinson Agents
- Anti-Dyskinesia Agents
- Memantine
Other Study ID Numbers
- HSR200202
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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