Coenzyme Q10 in Huntington's Disease

描述(申请人提供)：该研究的目标是确定辅酶Q10(CpQ)对亨廷顿病(HD)的疗效。虽然导致先天性心脏病的基因缺陷已经被确定，但目前还没有已知的有效治疗或治愈方法。亨廷顿病的合理治疗策略包括那些旨在改善细胞能量产生和减少氧化应激的策略。辅酶Q10，一种参与线粒体的辅因子！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存活时间。辅酶Q10每天600毫克，持续2年，与安慰剂相比，似乎可以减缓HD患者的功能衰退约13%。对辅酶Q的临床前和临床研究表明，更高的剂量更有益。研究假设是慢性辅酶Q对HD患者的治疗将减缓HD的进行性功能衰退。具体目的是通过对608名动态HD受试者进行一项双盲、安慰剂对照、随机、平行、多中心的CoQ研究来检验这一假设，每个受试者接受为期60个月的治疗。符合条件的受试者将随机服用辅酶Q2400 mg/d或匹配的安慰剂。根据HD、肌萎缩侧索硬化症和帕金森病的剂量范围耐受性研究，选择辅酶Q剂量为2400毫克。主要的预后指标将是HD的临床进展，通过基线和60个月之间总功能容量(TFC)的变化来衡量。次要措施将包括统一亨廷顿病分级标准(UHDRS)的其他临床分级标准的变化、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。

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.