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: 8236940
• 负责人: LYNNE H SHINTO
• 金额: $ 47.32万
• 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 2015-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8236940
• 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）：本研究的主要目的是评估硫辛酸与 omega-3 脂肪酸联合使用，在 18 个月内减缓阿尔茨海默病 (AD) 患者认知和功能衰退的能力。我们小组进行的一项试点研究结果表明，可能患有 AD 的参与者随机接受硫辛酸 (LA) 加 omega-3 脂肪酸 (n=13) 的平均简易精神状态检查 (MMSE) 评分和平均 ADL 下降幅度明显较小与安慰剂组相比，一年多的评分 (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 病理学生物标志物影响的初步数据。这项研究产生的数据将证明设计更大规模的临床试验的合理性，以更好地评估 LA 加 omega-3 脂肪酸治疗 AD 的临床效果。该研究被设计为一项随机、双盲、安慰剂对照试验。年龄在 55 岁或以上、被诊断患有疑似 AD、患有轻度至中度认知障碍 (MMSE 15-26) 的受试者将被纳入。一百名受试者将被随机分配接受 LA 加 omega-3 脂肪酸或安慰剂治疗，并继续治疗 18 个月。主要目标，目标 1，是评估减缓认知和功能衰退的治疗效果（通过阿尔茨海默氏病评估量表 - 认知分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，随机接受 LA 加 omega-3 脂肪酸治疗的患者认知功能和 ADL 下降幅度较小。目标 2 是收集 MRI 总脑体积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。目标 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；白细胞介素6；骨保护素；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。胰岛素抵抗稳态模型（HOMA-IR）将用于测量胰岛素抵抗的治疗效果。将确定这些标志物与临床结果之间的关联。这项研究旨在评估一种有可能延缓阿尔茨海默病认知和功能衰退的新疗法。 公共健康相关性：本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，因此科学评估这些疗法是一个重要的公共卫生问题。