The Use of Memantine for Prevention of Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Memantine hydrochloride
干预措施: Memantine Hydrochloride Tablets (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
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
时间窗: 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.
次要结局
- Intraclass correlation coefficient (ICC) for longitudinal follow-up(Baseline to 24 months)
- Summary of demographic characteristics of subjects overall, and in each arm.(Baseline to 24 months)
- Mean change in RBANS scores from baseline to end of protocol, overall and in each arm.(Baseline to 24 months)
研究者
Carol Manning
Professor of Neurology
University of Virginia