Coordination and Statistics for Coenzyme Q10 in Huntington's Disease

辅酶 Q10 在亨廷顿病中的协调和统计

• 批准号: 8710350
• 负责人: Michael P McDermott
• 金额: $ 78.61万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8710350
• 关键词: Activities of Daily Living; Address; Adverse event; Animal Model; Antioxidants; Biology; Biometry; Canis familiaris; Case Report Form; Chronic; Clinical; Clinical Research; Clinical Trials; Clinical Trials Data Monitoring Committees; Coenzyme Q10; Companions; Computational Biology; Consent; Data; Data Collection; Databases; Disclosure; Disease; Disease Progression; Doctor of Medicine; Dose; Double-Blind Method; Electron Transport; Electronics; Emergency treatment; Enrollment; Ensure; Environment; Evaluation; Event; Frequencies; Funding; Futility; General Hospitals; Generations; Goals; Human; Human Resources; Huntington Disease; Internet; Label; Laboratories; Maintenance; Manuals; Massachusetts; Measures; Medical center; Mitochondria; Modeling; Modification; Monitor; Mutation; National Institute of Neurological Disorders and Stroke; Outcome Measure; Outcome Study; Oxidative Stress; Participant; Patients; Pharmaceutical Preparations; Placebo Control; Placebos; Preparation; Procedures; Production; Property; Protocols documentation; Randomized; Reporting; Request for Applications; Research Infrastructure; Research Subjects; Resolution; Resources; Review Committee; Safety; Sampling; Secure; Serious Adverse Event; Site; Source; Standardization; Suspension substance; Suspensions; Testing; Therapeutic; Time; Toxicology; Training; Transgenic Mice; Universities; Visit; Withdrawal; base; clinically relevant; cofactor; data management; design; dosage; double-blind placebo controlled trial; effective therapy; follow-up; functional decline; improved; mouse model; operation; pre-clinical; premature; primary outcome; public health relevance; relational database; remacemide; statistics; trend

DESCRIPTION (provided by applicant): The study objective is to determine the efficacy of coenzyme Q10 (CoQ) in Huntington's disease (HD). Although the genetic defect that causes HD has been identified, there is no known effective treatment or cure. Rational therapeutic strategies in HD include those that are targeted to improving cellular energy production and reducing oxidative stress. Coenyzme Q10, a co-factor involved in mitochondrial electron transfer and an anti-oxidant, is a compound with these properties. Coenzyme Q10 slows progression and prolongs survival in a dose-dependent manner in a transgenic mouse model of HD. In a study in people with HD, CoQ at a dosage of 600 mg per day for 2 1/2 years appeared to slow the functional decline by approximately 13% compared to placebo. Pre-clinical and clinical studies with CoQ suggest that higher dosages are more beneficial. Toxicology studies were performed in dogs that supported proceeding with 2400 mg/day in people. The study hypothesis is that chronic treatment of HD patients with CoQ will slow the progressive functional decline of HD. The specific aim is to test this hypothesis by conducting a multi-center randomized, double-blind placebo-controlled, parallel group, study of CoQ involving 608 ambulatory HD subjects who are each treated for 60 months. Currently, 549 participants (90%) are enrolled and it is planned that enrollment will be completed by July 2012. The Data and Safety and Monitoring Committee reviewed the first futility analysis in August 2011 and recommended continuation of the study. Eligible subjects are randomized to CoQ 2400 mg/ day or a matching placebo. The primary outcome measure is the clinical progression of HD as measured by the change in total functional capacity (TFC) between baseline and 60 months. Secondary measures include changes in the other clinical rating scales of the Unified Huntington Disease Rating Scale, time to decline in TFC by 2 and 3 points, ability to complete the study at the assigned dosages and the frequencies of clinical and laboratory adverse events.

描述（由申请人提供）：研究目标是确定辅酶Q10（COQ）在亨廷顿氏病（HD）中的功效。尽管已经鉴定出导致HD的遗传缺陷，但尚无已知的有效治疗或治愈。 HD中的理性治疗策略包括针对改善细胞能量产生和减少氧化应激的治疗策略。 Coenyzme Q10是一种涉及线粒体电子转移和抗氧化剂的共同因素，是具有这些特性的化合物。辅酶Q10在HD的转基因小鼠模型中以剂量依赖性方式缓慢进展并延长生存。在一项针对HD患者的研究中，与安慰剂相比，在2 1/2年的每天剂量为600 mg的COQ降低了约13％。 COQ的临床前和临床研究表明，较高的剂量更有益。对毒理学研究进行了支持，该狗在支持2400毫克/天的人的狗中进行了毒理学研究。 该研究假设是，对HD患者的长期治疗将减缓HD的进行性功能下降。具体的目的是通过进行多中心随机，双盲安慰剂对照，并行组来检验这一假设，该研究涉及608个卧床高清受试者，这些受试者均经过60个月的治疗。目前，有549名参与者（90％）被录取，并计划在2012年7月之前完成招生。数据和安全和监测委员会审查了2011年8月的首次徒劳分析，并建议继续进行研究。合格的受试者被随机分为COQ 2400 mg/天或匹配的安慰剂。主要结局指标是基线到基线至60个月之间总功能能力（TFC）的变化测量HD的临床进展。次要措施包括统一亨廷顿疾病评级量表的其他临床评级量表的变化，TFC下降2和3点的时间，在指定的剂量上完成研究的能力以及临床和实验室不良事件的频率。