Coenzyme Q10 in Huntington's Disease

描述（由申请人提供）：研究目的是确定辅酶Q10 （CpQ）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，但没有已知的有效治疗或治愈方法。亨廷顿舞蹈病的合理治疗策略包括那些以改善细胞能量产生和减少氧化应激为目标的治疗策略。辅酶Q10，参与线粒体的辅助因子！电子转移和抗氧化剂，是一种具有这些性质的化合物。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。与安慰剂相比，每天服用600毫克辅酶Q10 2年似乎可以减缓HD的功能下降约13%。COQ的临床前和临床研究表明，更高的剂量更有益。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双盲、安慰剂对照、随机、平行组、多中心的CoQ研究来验证这一假设，该研究涉及608名流动HD受试者，每位受试者接受60个月的治疗。符合条件的受试者将被随机分配到CoQ 2400mg /天或匹配安慰剂组。根据对HD、肌萎缩性侧索硬化症和帕金森病的剂量范围耐受性研究，选择了2400 mg的CoQ剂量。主要结局指标将是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。次要指标将包括统一亨廷顿病评定量表（UHDRS）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 (CpQ) 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 Huntington's disease include those that are targeted to improving cellular energy production and reducing oxidative stress. Coenzyme Q10, a co-factor involved in mitochondria! electron transfer and an anti-oxidant, is a compound that has some of these properties. Coenzyme Q10 slows progression and prolongs survival in a dose dependent manner in a transgenic mouse model of HD. Coenzyme Q10 at a dosage of 600 mg per day for 2 years appeared to slowed the functional decline in HD by approximately 13% compared to placebo. Pre-clinical and clinical studies with COQ suggest that higher dosages are more beneficial. 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 double-blind, placebo-controlled, randomized, parallel group, multi-center study of CoQ involving 608 ambulatory HD subjects who are each treated for 60 months. Eligible subjects will be randomized to CoQ 2400 mg daily or matching placebo. A CoQ dosage of 2400 mg was chosen based on dosage ranging tolerability studies in HD, amyotrophic lateral sclerosis and Parkinson's disease. The primary outcome measure will be the clinical progression of HD as measured by the change in the total functional capacity (TFC) between baseline and 60 months. Secondary measures will include changes in the other clinical rating scales of the Unified Huntington Disease Rating Scale (UHDRS), times to decline in TFC by 2 and 3 points, ability to complete the study at the assigned dosage and the frequencies of clinical and laboratory adverse events.