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

描述(申请人提供)：这项研究的主要目标是评估硫辛酸和omega-3脂肪酸在18个月内延缓阿尔茨海默病(AD)患者认知和功能衰退的能力。我们小组进行的一项初步研究的结果显示，与安慰剂组(n=13)相比，随机服用硫辛酸(LA)和omega-3脂肪酸(n=13)的可能患有AD的参与者在1年内的平均MMSE分数和平均ADL分数的下降幅度显著小于安慰剂组(n=13)。这项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病理生物标记物的影响的初步数据。这项研究产生的数据将证明设计一项更大的临床试验是合理的，以更好地评估LA加omega-3脂肪酸治疗AD的临床有效性。这项研究是一项随机、双盲、安慰剂对照试验。被诊断为可能患有阿尔茨海默病、伴有轻度至中度认知损害(MMSE 15-26)的55岁或以上的受试者将被纳入研究对象。100名受试者将被随机分为LA加omega-3脂肪酸或安慰剂，并将继续治疗18个月。目标1的主要目标是评估对减缓认知和功能衰退的治疗效果(通过阿尔茨海默病评估量表-认知分量表和日常生活能力评估)。我们的假设是，与安慰剂组相比，随机接受LA加omega-3脂肪酸的患者认知功能和ADL下降较少。目的2是收集MRI总脑体积随时间的变化的初步数据，以评估这一测量作为治疗效果的潜在生物标记物的价值。目的3是收集一组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；护骨素；胆固醇；甘油三酯；低密度脂蛋白；高密度脂蛋白；24S-羟基胆固醇。胰岛素抵抗的稳态模型(HOMA-IR)将被用来衡量胰岛素抵抗的治疗效果。这些标记物和临床结果之间的关联将被确定。这项研究建议评估一种新的治疗方法，该方法有可能延缓阿尔茨海默病患者的认知和功能衰退。 与公众健康相关：这项研究将测试硫辛酸加omega-3脂肪酸治疗阿尔茨海默病的安全性和有效性。由于补充和替代医学疗法在美国被广泛使用，而人们对其中许多疗法的安全性和有效性知之甚少，因此科学地评估这些疗法是一个重要的公共卫生问题。

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.