Back to resultsThe Use of Memantine for Prevention of Alzheimer's Disease
Primary Purpose
Alzheimer Disease
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Memantine Hydrochloride Tablets
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Alzheimer Disease
Eligibility Criteria
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.
Sites / Locations
- University of VirginiaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Memantine hydrochloride
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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
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.
Secondary Outcome Measures
Summary of demographic characteristics of subjects overall, and in each arm.
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.
Mean change in RBANS scores from baseline to end of protocol, overall and in each arm.
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.
Intraclass correlation coefficient (ICC) for longitudinal follow-up
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05063851
Brief Title
The Use of Memantine for Prevention of Alzheimer's Disease
Official Title
The Use of Memantine for Prevention of Alzheimer's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 11, 2021 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Virginia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
Brief Summary
As the US population ages, the prevalence of dementia is increasing, and Alzheimer's Disease (AD) is the most prevalent one. Solving the Alzheimer's Disease (AD) epidemic is likely to require preventive therapy beginning many years before symptoms are expected to be evident in at-risk individuals. AD is caused by the dysfunction, loss of synapses, and eventual neuronal death, which may occur up to 25 years before clinical symptoms appear. This study, based off of pre-clinical data, seeks to assess whether it is feasible to use memantine hydrochloride for the prevention of Alzheimer's Disease.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Memantine hydrochloride
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Memantine Hydrochloride Tablets
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Baseline to 24 months
Secondary Outcome Measure Information:
Title
Summary of demographic characteristics of subjects overall, and in each arm.
Description
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.
Time Frame
Baseline to 24 months
Title
Mean change in RBANS scores from baseline to end of protocol, overall and in each arm.
Description
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.
Time Frame
Baseline to 24 months
Title
Intraclass correlation coefficient (ICC) for longitudinal follow-up
Description
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.
Time Frame
Baseline to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amy Fansler
Phone
434-243-1760
Email
acf7h@virginia.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carol Manning, PhD
Organizational Affiliation
Professor of Neurology
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anelyssa D'Abreu, MD
Organizational Affiliation
Associate Professor of Neurology
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kimberlee Meegan
Phone
434-243-2040
First Name & Middle Initial & Last Name & Degree
Carol Manning, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
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The Use of Memantine for Prevention of Alzheimer's Disease
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