Coordination and Statistics for Coenzyme Q10 in Huntington's Disease

描述（由申请人提供）：研究目的是确定辅酶Q10 （CoQ）在亨廷顿病（HD）中的疗效。虽然已经确定了导致HD的遗传缺陷，但目前还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。辅酶Q10是一种参与线粒体电子转移的辅助因子，也是一种抗氧化剂，是一种具有这些特性的化合物。在HD转基因小鼠模型中，辅酶Q10以剂量依赖的方式减缓进展并延长生存期。在一项针对HD患者的研究中，与安慰剂相比，每天服用600毫克CoQ，持续两年半，似乎可以减缓功能下降约13%。CoQ的临床前和临床研究表明，更高的剂量更有益。在狗身上进行的毒理学研究支持人类每天服用2400毫克。本研究假设对HD患者进行CoQ慢性治疗可以减缓HD的进行性功能衰退。具体目的是通过开展一项多中心随机、双盲、安慰剂对照、平行组的CoQ研究来验证这一假设，该研究涉及608名流动HD受试者，每个受试者接受60个月的治疗。目前，已有549名参与者（90%）注册，计划于2012年7月完成注册。数据、安全和监测委员会于2011年8月审查了第一次无效分析，并建议继续进行研究。符合条件的受试者被随机分配到CoQ 2400mg /天或匹配的安慰剂组。主要结局指标是HD的临床进展，通过基线至60个月间总功能容量（TFC）的变化来衡量。次要测量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和3点的时间，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。

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.