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）：本研究的主要目的是评估硫辛酸与ω-3脂肪酸联合治疗阿尔茨海默病（AD）患者在18个月内减缓认知和功能下降的能力。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，随机分配至硫辛酸（LA）加omega-3脂肪酸组（n= 13）的可能AD的参与者在1年内的平均简易精神状态检查（MMSE）评分和平均ADL评分下降明显较少。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。本研究生成的数据将证明设计更大规模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。本研究设计为随机、双盲、安慰剂对照试验。将入组55岁或55岁以上的受试者，诊断为可能患有AD，伴有轻度至中度认知损害（MMSE 15-26）。100名受试者将被随机分配至LA + omega-3脂肪酸组或安慰剂组，并将继续治疗18个月。主要目的（目的1）是评估对减缓认知和功能下降的治疗效果（通过阿尔茨海默病评估量表-认知子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总脑体积随时间变化的初步数据，以评价该指标作为治疗效果的潜在生物标志物。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;白细胞介素6;骨保护素;胆固醇;甘油三酯; LDL; HDL; 24 S-羟基胆固醇。胰岛素抵抗稳态模型（HOMA-IR）将用于测量对胰岛素抵抗的治疗效果。将确定这些标志物与临床结局之间的关联。这项研究旨在评估一种新的治疗方法，这种方法有可能延缓阿尔茨海默病的认知和功能下降。 公共卫生相关性：这项研究将测试硫辛酸加omega-3脂肪酸在阿尔茨海默病中的安全性和有效性。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。