Lipoic Acid and Omega-3 Fatty Acids in Alzheimer's Disease

描述（由申请人提供）：本研究的主要目的是评估硫辛酸联合omega-3脂肪酸在阿尔茨海默病（AD）患者18个月内减缓认知和功能衰退的能力。我们小组进行的一项初步研究结果显示，与安慰剂组（n=13）相比，可能患有AD的参与者随机分配到硫辛酸（LA）加omega-3脂肪酸组（n=13）， 1年内平均迷你精神状态检查（MMSE）评分和平均ADL评分的下降幅度明显小于安慰剂组（n=13）。拟议的研究将是一项试点试验，旨在收集LA加omega-3脂肪酸对认知功能、ADL和AD病理生物标志物的影响的初步数据。该研究产生的数据将为设计更大规模的临床试验提供依据，以更好地评估LA + omega-3脂肪酸治疗AD的临床效果。该研究设计为随机、双盲、安慰剂对照试验。受试者年龄在55岁或以上，诊断为可能患有AD，伴有轻度至中度认知障碍（MMSE 15-26）。100名受试者将被随机分为LA + omega-3脂肪酸组或安慰剂组，并将持续治疗18个月。主要目的是评估治疗对减缓认知和功能衰退的效果（通过阿尔茨海默病评估量表-认知亚量表和日常生活活动进行评估）。我们的假设是，与安慰剂组相比，那些随机接受LA加omega-3脂肪酸的患者在认知功能和ADL方面的下降幅度较小。目的2是收集MRI总脑容量随时间变化的初步数据，以评估该测量作为治疗效果的潜在生物标志物。目的3：收集血清和血浆生物标志物的初步数据：肿瘤坏死因子α；白介素6;osteoprotegerin;胆固醇;甘油三酸酯;低密度脂蛋白;高密度脂蛋白;24 s-hydroxycholesterol。胰岛素抵抗稳态模型（HOMA-IR）将用于测量治疗对胰岛素抵抗的影响。这些标志物与临床结果之间的关联将被确定。本研究提出评估一种新的治疗方法，有可能延缓阿尔茨海默病的认知和功能衰退。

DESCRIPTION (provided by applicant): The main objective of this study is to assess the ability of lipoic acid combined with omega-3 fatty acids in slowing cognitive and functional decline over 18 months in people with Alzheimer's disease (AD). Results from a pilot study conducted by our group showed that participants with probable AD randomized to lipoic acid (LA) plus omega-3 fatty acids (n=13) had significantly less decline in mean Mini Mental State Examination (MMSE) score and mean ADL score over 1-year compared to those in the placebo group (n=13). The proposed study will be a pilot trial designed to collect preliminary data on the effects of LA plus omega-3 fatty acids on cognitive function, ADL, and biomarkers of AD pathology. Data generated from this study would justify the design of a larger clinical trial to better assess the clinical effectiveness of LA plus omega-3 fatty acids in AD. The study is designed as a randomized, double-blind, placebo-controlled trial. Subjects 55 years or older diagnosed with probable AD, with mild to moderate cognitive impairment (MMSE 15-26) will be enrolled. One hundred subjects will be randomized to LA plus omega-3 fatty acids or placebo and will continue treatment for 18 months. The primary objective, Aim 1, is to assess treatment effect on slowing cognitive and functional decline (assessed by Alzheimer's Disease Assessment Scale - Cognitive Subscale and by Activities of Daily Living). Our hypothesis is that those randomized to receive LA plus omega-3 fatty acids will have less decline in cognitive function and ADL compared to the placebo group. Aim 2, is to collect preliminary data on changes in MRI total brain volume over time to evaluate this measure as a potential biomarker for treatment effect. Aim 3, is to collect preliminary data on a panel of serum and plasma biologic markers: tumor necrosis factor alpha; interleukin 6; osteoprotegerin; cholesterol; triglycerides; LDL; HDL; 24S-hydroxycholesterol. Homeostasis Model of Insulin Resistance (HOMA-IR) will be used to measure treatment effects on insulin resistance. Associations between these markers and clinical outcomes will be determined. This study proposes to evaluate a novel treatment that has the potential to delay cognitive and functional decline in Alzheimer's disease. PUBLIC HEALTH RELEVANCE: This study will test the safety and effectiveness of lipoic acid plus omega-3 fatty acids in Alzheimer's disease. Because complementary and alternative medicine therapies are widely used in the U.S. and little is know about the safety and effectiveness of many of these therapies, it is an important public health issue to scientifically evaluate these therapies.