CSP #546 - A Randomized, Clinical Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 613
- 试验地点
- 14
- 主要终点
- Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS/ADL) Inventory Change From Baseline
研究概览
简要总结
The purpose of this study is to determine whether alpha-tocopherol, memantine (Namenda), or the combination will significantly delay clinical progression in mild to moderately demented patients with Alzheimer's disease compared to placebo.
详细描述
Abstract: Alzheimer's disease (AD), a neurodegenerative disorder resulting in cognitive loss, behavioral problems, and functional decline, is characterized by well-established and well-known neuropathological changes in the brain. Cognitive deficits and behavioral symptoms are thought to be due to cholinergic neuronal degeneration and loss associated with oxidative stress and inflammatory responses.
Current therapeutic strategies include efforts to
- enhance cholinergic neuronal function,
- promote neuroprotective effects, and
- block pathologic activity of excessive glutamate with a moderate-affinity NMDA antagonist.
A combination of pharmacological therapies directed at simultaneously improving neuronal function and neuroprotection would presumably be more effective than either treatment alone.
To test this hypothesis, this study will examine the efficacy of drug treatment with a combination of
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnoses of possible or probable Alzheimer's disease (NINCDS-ADRDA)
- •Presence of a caregiver (friend or relative) who can assume responsibility for medication compliance, can accompany the patient to all visits, and rate patient's condition
- •Written informed consent from both the patient (or surrogate) and caregiver
- •An MMSE score between 12 and 26 inclusive
- •Administration of a maintenance dosage of donepezil (5-10mg/d), rivastigmine (6-12mg/d) or rivastigmine (Exelon) patch (4.6 mg or 9.5 mg), galantamine or galantamine ER (16-24mg/d) for a minimum of 4 weeks prior to randomization
- •Agreement not to take vitamin E supplements and/or memantine outside of the study (daily multivitamin is permitted containing up to 100 IU alpha-tocopherol)
排除标准
- •A non-Alzheimer primary dementia (e.g., vascular dementia, Lewy body dementia, fronto-temporal dementia, vitamin B-12 deficiency, hypothyroidism)
- •Current major depression, delirium, alcohol or psychoactive substance abuse or dependency, schizophrenia, or delusional disorder as defined by DSM-IV
- •Presence of any uncontrolled systemic illness that would interfere with participation in the study or a life expectancy of less than one year
- •Pregnant or intention to become pregnant
- •Enrollment in another interventional clinical trial
- •Current prescription with more than one AChE inhibitor
- •Current prescription for warfarin
- •Use of vitamin E supplements in the past 2 weeks
- •Use of memantine in the past 4 weeks or known intolerance
- •Estimated creatinine clearance less than 5ml/min (Cockcroft-Gault formula)
- •Use of amantadine in the past 2 weeks
研究组 & 干预措施
Arm 1
2,000 IU per day of dl-alpha-tocopherol plus placebo for memantine
干预措施: dl-alpha-tocopherol (Drug)
Arm 2
20 mg per day of memantine plus placebo for dl-alpha-tocopherol
干预措施: Memantine (Drug)
Arm 3
Combination of 2,000 IU per day of dl-alpha-tocopherol and 20 mg per day of memantine
干预措施: dl-alpha-tocopherol (Drug)
Arm 3
Combination of 2,000 IU per day of dl-alpha-tocopherol and 20 mg per day of memantine
干预措施: Memantine (Drug)
Arm 4
Matching placebos for dl-alpha-tocopherol and memantine
干预措施: Placebo (Drug)
结局指标
主要结局
Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS/ADL) Inventory Change From Baseline
时间窗: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline
The primary outcome of the study was the Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS/ADL) Inventory. The ADCS/ADL Inventory is designed to assess functional abilities to perform activities of daily living in Alzheimer patients with a broad range of dementia severity. The total score ranges from 0 to 78 with higher scores indicating greater abilities. Outcome analysis is average least square means change from baseline.
Mini-Mental State Examination Change From Baseline
时间窗: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline
The Mini-Mental State Examination (MMSE) briefly and objectively assess cognitive status in psychiatric patients with cognitive impairment. The MMSE questions are grouped into seven categories, each representing a different cognitive domain. The MMSE yields a total score that ranges from 0 for a patient who gives no correct response to a score of 30 for a patient who makes no errors. Outcome analysis is average least square means change from baseline.
Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog) Change From Baseline
时间窗: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline
The Alzheimer's Disease Assessment Scale (ADAS) is a 21-item scale designed to assess the severity of cognitive and non-cognitive behavioral impairments in patients with Alzheimer's disease. The cognitive portion of the scale (ADAS-cog) consists of 11 items to assess memory, language, and praxis functions. The ADAS-cog total score ranges from 0 (no errors) to 70 (severe cognitive impairment). Outcome analysis is average least square means change from baseline.
Neuropsychiatric Inventory Change From Baseline
时间窗: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline
The Neuropsychiatric Inventory (NPI) assesses psychological and behavioral problems in patients with dementia. For each of twelve domains, there are four scores: frequency, severity, total frequency x severity, and caregiver distress. The frequency x severity total scores from each domain are summed for an overall total score that ranges from 0 to 144. The total caregiver distress scores are also summed for an overall total caregiver distress score that ranges from 0 to 60. The secondary endpoint for the trial will be the overall frequency times severity total score. Outcome analysis is average least square means change from baseline.
Caregiver Activity Survey Change From Baseline
时间窗: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline
The Caregiver Activity Survey (CAS) was developed to measure the time caregivers spend aiding Alzheimer patients with their day-to-day activities. The CAS consists of six items that ask for an estimate in hours and minutes of the time that the caregiver spent during the previous 24 hours performing these particular activities. The six CAS items are as follows: 1) communication with the person, 2) using transportation, 3) dressing, 4) eating, 5) looking after one's appearance, and 6) supervising the person. The more caregiving hours the worse the patient's functioning level. Outcome analysis is average least square means change from baseline.
次要结局
- Dependence Scale: Time to Event Analysis (Increase of of One Dependence Level)(Every 6 months to a maximum of 4 years)