Fish oil & alpha lipoic acid in mild Alzheimer's disease

鱼油

• 批准号: 6804713
• 负责人: LYNNE H SHINTO
• 金额: $ 17.96万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6804713
• 关键词: Alzheimer' s disease; acute phase protein; antioxidants; brain disorder chemotherapy; clinical research; clinical trials; cognition disorders; diet therapy; dietary supplements; human middle age (35-64); human old age (65+); human subject; human therapy evaluation; inflammation; marine animal oil; nutrition related tag; oxidative stress; patient oriented research; quality of life

DESCRIPTION (provided by applicant): The heterogeneous nature of the biological mechanisms associated with Alzheimer's disease (AD) pathology make therapies that can target multiple mechanisms of action rather than a single mechanism attractive candidates to delay or prevent disease progression. Oxidative stress has been highly implicated in Alzheimer's disease pathology and recent studies show there is also an association between an increase in inflammation and cholesterol (respectively), and AD pathology. Fish oil and alpha lipoic also have the ability to decrease oxidative stress, inflammation, and lipid levels, making them strong candidates as therapeutic agents in slowing the progression of Alzheimer's disease. These supplements also have few reported side effects. Based on their mechanisms of action, a combination of the two supplements has the potential to maximize the therapeutic benefit in delaying the progression in AD. The proposed study will be a pilot trial designed to collect preliminary data to aid in the design of a larger clinical trial powered to assess both treatments' effect on mechanisms associated with AD pathology and clinical markers of AD pathology. This pilot study is designed as a 3-arm, parallel group, double-blind placebo-controlled trial. Subjects >55 yrs. diagnosed with probable AD and having mild cognitive impairment will be randomized to one of three groups (13 subjects/group): 1. fish oil alone, 2. fish oil plus alpha lipoic acid, 3. placebo. The treatment intervention will be for 1-year. Our primary objective, Aim 1, is to assess the treatments' effect on oxidative stress by measuring urine F2-isoprotane levels. We will also collect preliminary data on the treatments' effect on plasma lipid levels and high-sensitivity C-reactive protein. Our secondary objective, Aim 2, is to collect preliminary data on AD-related clinical outcome measures which will include: the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Clinical Dementia Rating scale (CDR), Mini Mental State Examination (MMSE), Alzheimer's Disease Cooperative Study Activities of Daily Living Scale, SF-36, and Logical Memory I1.Our tertiary objective, Aim 3, is to assess treatment safety by a monthly monitoring of adverse events and laboratory tests (metabolic panel, including liver function tests and platelet function assay). Compliance of fish oil supplementation will be assessed by red blood cell membrane fatty acid analysis.

描述（由申请人提供）：与阿尔茨海默病（AD）病理学相关的生物机制的异质性使得能够针对多种作用机制而不是单一机制的疗法成为延迟或预防疾病进展的有吸引力的候选者。氧化应激与阿尔茨海默病的病理学密切相关，最近的研究表明，炎症和胆固醇的增加（分别）与阿尔茨海默病的病理学之间也存在关联。鱼油和α-硫辛酸还具有降低氧化应激、炎症和脂质水平的能力，使其成为减缓阿尔茨海默病进展的有力候选治疗剂。这些补充剂也几乎没有副作用报道。根据它们的作用机制，这两种补充剂的组合有可能最大限度地发挥延缓 AD 进展的治疗效果。拟议的研究将是一项试点试验，旨在收集初步数据，以帮助设计更大规模的临床试验，以评估两种治疗方法对 AD 病理学相关机制和 AD 病理学临床标志物的影响。该试点研究被设计为三组、平行组、双盲安慰剂对照试验。受试者 >55 岁。被诊断患有疑似 AD 并患有轻度认知障碍的患者将被随机分为三组（13 名受试者/组）之一：1. 单独使用鱼油，2. 鱼油加 α 硫辛酸，3. 安慰剂。治疗干预为期1年。我们的主要目标（目标 1）是通过测量尿液 F2-异丙烷水平来评估治疗对氧化应激的影响。我们还将收集有关治疗对血脂水平和高敏 C 反应蛋白影响的初步数据。我们的次要目标，目标 2，是收集 AD 相关临床结果测量的初步数据，其中包括：阿尔茨海默病评估量表认知分量表 (ADAS-cog)、临床痴呆评定量表 (CDR)、简易精神状态检查 ( MMSE）、阿尔茨海默病合作研究活动量表、SF-36 和逻辑记忆 I1。我们的第三个目标，目标 3，是通过每月监测来评估治疗安全性不良事件和实验室测试（代谢组，包括肝功能测试和血小板功能测定）。鱼油补充的依从性将通过红细胞膜脂肪酸分析来评估。