Alzheimer's Disease in Down Syndrome: Antioxidant Trial

唐氏综合症中的阿尔茨海默病：抗氧化剂试验

• 批准号: 6893393
• 负责人: IRA T. LOTT
• 金额: $ 36.96万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6893393
• 关键词: Alzheimer' s disease; Downs syndrome; acetylcholinesterase; amyloid proteins; antioxidants; ascorbate; biomarker; carbonyl group; clinical research; clinical trials; cognition; dietary supplements; enzyme inhibitors; glutathione; human subject; human therapy evaluation; lipid peroxides; longitudinal human study; nutrition related tag; oxidative stress; patient oriented research; questionnaires; therapy compliance; tocopherols; vitamin therapy

DESCRIPTION (provided by applicant): The objective of this pilot clinical trial is to obtain information on the tolerability, safety, and efficacy of a high potency combinatorial supplement in the treatment of Alzheimer disease (AD) in Down syndrome (DS). Individuals with DS have an increased incidence of AD and evidence of oxidative stress in brain. The DS population is an excellent candidate for antioxidant intervention. The trial will conform to a double-blind, placebo-controlled, and repeated analysis of variance design. The supplement will consist two cellular antioxidants (vitamins E 900 IU/day and C 200 mg/day) and a mitochondrial antioxidant (alpha-lipoic acid 600 mg/day). The clinical diagnosis of AD in DS will be made by the investigators utilizing their previous experience with DSM-IV criteria for dementia in DS. There are three specific aims: 1) to determine whether cognitive measures are improved by antioxidant supplementation. Outcome measures have been shown to have reliability and validity for DS. They comprise three informant scales (Dementia Rating Scale for Persons with Mental Retardation, Neuropsychology Behavior and Affect Profile, Vineland Adaptive Scales) and three direct assessments (Severe Impairment Battery, Brief Praxis Test, and the FULD-Object/Memory Test-modified); 2) to determine whether plasma biomarkers of lipid oxidative damage (malondialdehyde, isoprostanes), protein oxidative damage (carbonyl group formation), levels of beta-amyloid, and vitamin E levels will be altered in subjects receiving the diet; and 3) to determine the safety and tolerability of the antioxidant supplementation utilizing checklists for adverse events, clinical chemistries, and measures of medication compliance. All study measures will be obtained at baseline and at 6-month intervals for a total of 24 months of treatment. All study patients will be on an acetylcholinesterase inhibitor. Power analysis configured on the primary outcome measures supports a study group of 30 treated and 30 placebo randomized patients. Database management will facilitate analysis of the 24-month observations. The data from this study is intended to provide information relevant to the indications for a multicenter definitive clinical trial of antioxidants in DS. Since the process resulting in AD in DS is age dependent across the lifespan, a positive result from this pilot trial may have implications for utilizing high potency combinatorial antioxidants at earlier age epochs in DS. The pilot trial should also contribute information as to the possible role of antioxidants in the treatment or prevention of AD in the general population.

描述（由申请人提供）：这项试验临床试验的目的是获取有关高效力组合补充剂在阿尔茨海默氏病（AD）治疗唐氏综合症（DS）中的耐受性，安全性和功效的信息。 DS患者的AD发生率增加，并且大脑中氧化应激的证据。 DS人群是抗氧化剂干预的极好候选者。该试验将符合双盲，安慰剂对照，并重复对方差设计分析。该补充剂将构成两种细胞抗氧化剂（维生素E 900 IU/天和C 200 mg/天）和线粒体抗氧化剂（α-脂肪酸600 mg/day）。 DS中AD的临床诊断将由研究人员利用其先前在DS中具有DSM-IV标准的经验。有三个特定的目的：1）确定是否通过补充抗氧化剂来改善认知措施。结果指标已显示为DS具有可靠性和有效性。它们包括三个线人量表（具有智力低下的人，神经心理学行为和影响概况的人的痴呆评级量表，Vineland自适应量表）和三个直接评估（严重的损伤电池，简短的PRAXIS测试以及Fuld-Object/Morement/Memory Test Test-Rodified）； 2）确定脂质氧化损伤的等离子体生物标志物（丙二醛，异丙醛），蛋白质氧化损伤（羰基组），β-淀粉样蛋白的水平和维生素E水平是否会改变接受饮食的受试者； 3）确定补充抗氧化剂的安全性和耐受性，利用清单进行不良事件，临床化学和药物依从性测量。所有研究措施将在基线和6个月的间隔中获得24个月的治疗。所有研究患者将使用乙酰胆碱酯酶抑制剂。在主要结果指标上配置的功率分析支持30例治疗和30个安慰剂随机患者的研究组。数据库管理将有助于分析24个月的观察结果。这项研究的数据旨在提供与DS中抗氧化剂的多中心确定性临床试验相关的信息。由于DS中导致AD的过程取决于整个寿命的年龄，因此该试验试验的积极结果可能对在DS中早期时代使用高效力组合抗氧化剂有影响。试点试验还应为抗氧化剂在普通人群中的治疗或预防AD治疗中的可能作用提供信息。