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

硫辛酸和 Omega-3 脂肪酸在阿尔茨海默病中的作用

• 批准号: 8049187
• 负责人: LYNNE H SHINTO
• 金额: $ 50.58万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8049187
• 关键词: Activities of Daily Living; Alzheimer' s Disease; Atrophic; Attention; Auditory; Behavior; Beta Cell; Biological Markers; Biological Markers; Blood; Blood Glucose; Brain; Caring; Cell physiology; Cholesterol; Clinical; Clinical Markers; Clinical Trials; Clinical Trials Design; Clinical effectiveness; Cognition; Cognitive; Complementary and alternative medicine; Data; Diagnosis; Disease; Disease Outcome; Disease Progression; Effectiveness; Enrollment; Equipment and supply inventories; Fasting; Fish Oils; Functional disorder; Future; Gold; Healthcare; High Density Lipoproteins; Homeostasis; Hydroxycholesterols; Hyperglycemia; Impaired cognition; Incidence; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Learning; Lipids; Low-Density Lipoproteins; Magnetic Resonance Imaging; Measures; Memory; Methods; Modeling; Omega-3 Fatty Acids; Outcome; Outcome Measure; Participant; Pathology; Pilot Projects; Placebos; Plasma; Prevalence; Public Health; Quality of life; Randomized; Regulation; Safety; Serum; Supplementation; Therapeutic; Therapeutic Agents; Thioctic Acid; Time; Trail Making Test; Triglycerides; Tumor Necrosis Factor-alpha; Tumor necrosis factor receptor 11b; Vascular Diseases; Verbal Learning; brain volume; cerebral atrophy; cognitive function; cost; design; double-blind placebo controlled trial; executive function; functional decline; improved; indexing; inflammatory marker; insulin sensitivity; low density lipoprotein triglyceride; mental state; neuropsychiatry; novel; pilot trial; prevent; primary outcome; public health relevance; safety testing; treatment effect

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.

描述（由申请人提供）：这项研究的主要目的是评估lipoic酸与omega-3脂肪酸在阿尔茨海默氏病（AD）中在18个月内放缓认知和功能下降的能力。我们小组进行的一项试点研究的结果表明，可能AD的参与者随机分配给脂酸（LA）加omega-3脂肪酸（n = 13）的平均迷你心理检查（MMSE）得分和平均ADL的下降明显较小。与安慰剂组相比，得分超过1年（n = 13）。拟议的研究将是一项试点试验，旨在收集有关LA Plus Omega-3脂肪酸对AD病理学认知功能，ADL和生物标志物的影响的初步数据。这项研究产生的数据将证明一项更大的临床试验的设计是合理的，以更好地评估LA Plus Omega-3脂肪酸在AD中的临床有效性。该研究被设计为一项随机，双盲，安慰剂对照试验。被诊断为可能AD的55岁或以上的受试者将招募轻度至中度认知障碍（MMSE 15-26）。一百名受试者将被随机分为LA Plus Omega-3脂肪酸或安慰剂，并将继续治疗18个月。 AIM 1的主要目标是评估对认知和功能下降减慢的治疗效果（由阿尔茨海默氏病评估量表评估 - 认知量表和日常生活活动）。我们的假设是，与安慰剂组相比，那些随机接收LA Plus Omega-3脂肪酸的认知功能和ADL的下降将较少。目标2是收集有关MRI随时间变化的初步数据，以评估该措施作为治疗效果的潜在生物标志物。目标3是在血清和血浆生物学标记面板上收集初步数据：肿瘤坏死因子α；白介素6;骨蛋白酶蛋白；胆固醇;甘油三酸酯； ldl; hdl; 24S-羟基胆固醇。胰岛素抵抗（HOMA-IR）的稳态模型将用于测量对胰岛素抵抗的治疗作用。这些标记与临床结果之间的关联将得到确定。这项研究建议评估一种新的治疗方法，该治疗方法有可能延迟阿尔茨海默氏病的认知和功能下降。 公共卫生相关性：这项研究将测试lipoic Acid和Omega-3脂肪酸在阿尔茨海默氏病中的安全性和有效性。由于在美国广泛使用了补充和替代医学疗法，而且对许多疗法的安全性和有效性知之甚少，因此科学评估这些疗法是一个重要的公共卫生问题。