Creatine Safety and Efficacy in HD: Coordination and Statistical Supplement

描述（由申请人提供）：本申请要求为肌酸治疗亨廷顿病（HD）的III期临床试验的研究协调、数据管理和生物统计支持提供资金。这是Steven M. Hersch，MD，PhD，来自马萨诸塞州总医院（MGH），题为肌酸安全性、耐受性和功效（CREST-E）。HD是一种常染色体显性遗传、一致进行性神经退行性疾病，临床特征为运动障碍、人格改变和认知障碍。 在美国大约有30，000人有HD的临床表现，另外150，000名健康人被认为有发生HD的直接风险。没有有效的治疗HD和HD进展无情地造成残疾和死亡。来自HD小鼠模型和人类研究的证据表明，肌酸可能以剂量依赖性方式减缓HD的病程。关于血清和大脑生物利用度、耐受性、HD体征和症状以及生物标志物的初步数据表明，每日30克肌酸是最佳剂量。 我们建议在650名有症状的HD患者中进行一项随机、双盲、安慰剂对照、平行组试验，每天30克肌酸，以检验肌酸可以减缓HD下降的假设。主要结局变量为总功能能力（TFC）评分从基线至第36个月的变化。本研究将有96%的把握度检测临床相关的TFC减慢25%。该试验将在亨廷顿研究小组（HSG）的主持下在全球约42家研究中心进行。 这个项目是符合NCCAM的使命探索替代疗法，如肌酸与科学严谨的研究。这项研究具有重要的公共卫生意义。如果这项研究是积极的，这将是HD研究的一个突破，将改变HD的临床护理，并将刺激对许多相关神经退行性疾病的类似化合物的研究。此外，该研究将提供有关高剂量肌酸长期安全性的关键信息，肌酸广泛用于健康运动员和患有各种神经退行性疾病和其他疾病的患者。这将使NCCAM能够向公众发布有关肌酸安全性的权威信息。

DESCRIPTION (provided by applicant): This application requests funding for the study coordination, data management, and biostatistical support for a Phase III clinical trial of creatine in Huntington's disease (HD). This is a companion application to that of Steven M. Hersch, MD, PhD, from Massachusetts General Hospital (MGH), entitled Creatine Safety, Tolerability & Efficacy (CREST-E). HD is an autosomal dominant, uniformly progressive neurodegenerative disorder characterized clinically by movement disorders, personality changes, and cognitive impairment. Approximately 30,000 people in the United States have clinical manifestations of HD, and an additional 150,000 healthy people are thought to be at immediate risk for developing HD. There are no effective treatments for HD and HD progresses relentlessly causing disability and death. Evidence from mouse models of HD and human studies suggests that creatine may slow the course of HD in a dose dependent manner. Pilot data on serum and brain bioavailability, tolerability, HD signs and symptoms, and biomarkers indicate that 30-grams daily of creatine is an optimal dose. We propose to test the hypothesis that creatine can slow the decline of HD by conducting a randomized, double-blinded, placebo-controlled, parallel group trial of 30 grams daily of creatine in 650 symptomatic individuals with HD. The primary outcome variable will be the change from baseline to Month 36 in the Total Functional Capacity (TFC) score. The study will have 96% power to detect a clinically relevant 25% slowing in TFC. The trial will be conducted under the auspices of the Huntington Study Group (HSG) at approximately 42 sites worldwide. This project is consistent with the NCCAM mission of exploring alternative therapies such as creatine with scientifically rigorous studies. There are important public health implications of this study. If the study is positive, it would be a breakthrough in HD research that would change HD clinical care and would spur research into similar compounds for a host of related neurodegenerative diseases. Additionally, the study will provide critical information on the long-term safety of high dose creatine, which is widely used among healthy athletes and patients with a variety of neurodegenerative disorders and other diseases. This will allow NCCAM to distribute authoritative information to the public about the safety of creatine.