A Randomized Double-Blind Placebo-Controlled Trial Of The Effects Of Docosahexaenoic Acid (DHA) In Slowing The Progression Of Alzheimer's Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 402
- 试验地点
- 51
- 主要终点
- Rate of Change on the ADAS-Cog 11.
研究概览
简要总结
The purpose of this study is to determine whether chronic DHA (Docosahexaenoic Acid) supplementation slows the progression of cognitive and functional decline in mild to moderate Alzheimer's disease (AD).
详细描述
Preliminary studies have shown a reduced risk of Alzheimer's disease (AD) in people consuming increased amounts of fish in their diets. Many of the health benefits of fish are attributed to the abundance of omega 3 fatty acids. Docosahexaenoic Acid (DHA) is the most abundant omega 3 fatty acid in the brain. Data from several animal models supports the hypothesis that DHA may be an effective treatment for AD by means of anti-amyloid, antioxidant, and neuroprotectant mechanisms.
In this study, 400 individuals with mild to moderate AD will participate at approximately 53 study sites throughout the US for 18 months. Participants will be randomized so that 60% will receive approximately 2 grams of DHA, divided into 4 capsules, 2 capsules taken twice a day, while 40% receive an identical placebo.
Potential participants will go to their study site for a screening visit, where eligibility is determined, and if accepted, for a baseline visit where cognitive status, behavioral status, functional status, and global severity of dementia will be assessed. Vital signs and biomarker labs will also be obtained. Subsequent visits will occur every three months for medication checks and, every 6 months, further assessments, physical exams, and labs.
Some participants will also take part in MRI (magnetic resonance imaging) and/or CSF (cerebrospinal fluid) sub-studies. For the MRI sub-study, scans will be done prior to beginning the study medication, and again after 18 months. Likewise, for the CSF sub-study, a lumbar puncture will be done prior to beginning the study medication, and again after 18 months.
Enrollment is restricted to individuals who consume no more than 200 mg of DHA per day, which is almost 300% of the average daily intake in an American diet. Individuals who take fish oil or omega 3 fatty acid supplements are also not eligible. Each visit will include completion of a very brief food frequency questionnaire to monitor dietary DHA levels.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female
- •50 years of age or older
- •Residing in the community at baseline (includes assisted living facilities, but excludes long-term care nursing facilities)
- •MMSE (Mini-Mental State Examination) at screen of 14-26 (inclusive)
- •No medical contraindications to study participation
- •Fluent in English or Spanish
- •Corrected vision and hearing sufficient for compliance with testing procedures
- •Supervision available for study medication
- •Caregiver/study partner to accompany participant to all visits
- •Study partner must have direct contact with the participant more than 2 days/week
- •Able to ingest oral medication
- •Daily DHA consumption less than or equal to 200 mg/day in prior two months estimated by an abbreviated DHA food frequency questionnaire
- •Neuroimaging consistent with the diagnosis of AD at some time after the onset of the memory decline
- •Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the investigator
- •Stable use of cholinesterase inhibitors and memantine is permitted if doses are stable for 4 months prior to enrollment
排除标准
- •Non-AD dementia
- •Residence in a long-term care facility at baseline
- •History of clinically significant stroke
- •Modified Hachinski Ischemia score ≥ 4
- •Current evidence or history in past two years of epilepsy, seizure, focal brain lesion, head injury with loss of consciousness or DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
- •Sensory impairment which would prevent subject from participating in or cooperating with the protocol
- •Use of another investigational agent within two months
- •Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving an investigational new drug including clinically significant or unstable hematologic, hepatic, cardiovascular (including history of ventricular fibrillation or ventricular tachycardia), pulmonary, gastrointestinal, endocrine, metabolic, renal, or other systemic disease or laboratory abnormality
- •Active neoplastic disease (skin tumors other than melanoma may be included; participants with stable prostate cancer may be included at the discretion of the Project Director)
研究组 & 干预措施
1.
DHA
干预措施: DHA (Docosahexaenoic Acid) (Drug)
2.
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Rate of Change on the ADAS-Cog 11.
时间窗: Baseline, 6, 12, 18 months
ADAS-cog 11 = Alzheimer's Disease Assessment Scale, cognitive sub-scale in points per year. This is a psychometric measure sensitive to change in mild to moderate AD. The range of this instrument is 0 to 70 with higher numbers indicating greater impairment.
Rate of Change on CDR-SOB
时间窗: 18 months
CDR-SOB = Clinical Dementia Rating, Sum of Boxes. This is a global rating of dementia severity based on the clinician's interpretation of the history and examination. The range of this instrument is 0 to 18 with higher numbers indicating greater impairment.
次要结局
- Neuropsychiatric Inventory (NPI)(18 months)
- ADCS-ADL(18 months)