Coordination and Statistics for Coenzyme Q10 in Huntington's Disease

描述（由申请方提供）：研究目的是确定辅酶Q10（CoQ）在亨廷顿病（HD）中的疗效。虽然导致HD的遗传缺陷已被确定，但没有已知的有效治疗或治愈方法。HD的合理治疗策略包括以改善细胞能量产生和减少氧化应激为目标的治疗策略。Coenyzme Q10是一种参与线粒体电子转移的辅助因子和抗氧化剂，是具有这些特性的化合物。辅酶Q10以剂量依赖性方式减缓HD转基因小鼠模型的进展和存活。在HD患者的一项研究中，与安慰剂相比，每天600 mg剂量的CoQ持续2年半似乎减缓了约13%的功能下降。辅酶Q的临床前和临床研究表明，更高的剂量更有益。在犬中进行了毒理学研究，支持在人中继续使用2400 mg/天。 研究假设是，用辅酶Q长期治疗HD患者将减缓HD的进行性功能下降。具体目的是通过进行一项多中心、随机、双盲、安慰剂对照、平行组的辅酶Q研究来检验这一假设，该研究涉及608例接受60个月治疗的非卧床HD受试者。目前，549名参与者（90%）已入组，计划将于2012年7月完成入组。数据、安全性和监查委员会于2011年8月审查了首次无效性分析，并建议继续进行研究。合格的受试者被随机分配至辅酶Q 2400 mg/天或匹配的安慰剂组。主要结局指标是HD的临床进展，通过基线和60个月之间总功能容量（TFC）的变化进行测量。次要指标包括统一亨廷顿病评定量表的其他临床评定量表的变化、TFC下降2分和3分的时间、在指定剂量下完成研究的能力以及临床和实验室不良事件的频率。 公共卫生相关性：尽管对亨廷顿氏病（HD）病因的了解取得了进展，但仍没有已知的有效治疗或治愈方法。Coenyzme Q10已在HD动物模型中证明有效，并且先前已证明可能减缓人类疾病进展。任何减缓疾病进程的化合物都将具有直接的临床意义，本研究的积极结果将增强我们对HD潜在生物学的理解。

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. PUBLIC HEALTH RELEVANCE: Despite advances in understanding the cause of Huntington's disease (HD), there is no known effective treatment or cure. Coenyzme Q10 has demonstrated efficacy in an animal model of HD and was previously shown to possibly slow disease progression in people. Any compound that slows disease course will have immediate clinical importance, and a positive outcome of this study will enhance our understanding of the underlying biology of HD.