Creatine Safety and Efficacy in HD: Coordination and Statistical Center

描述(由申请人提供)：本申请请求为肌酸治疗亨廷顿病(HD)的第三阶段临床试验的研究协调、数据管理和生物统计学支持提供资金。这是马萨诸塞州综合医院(MGH)史蒂文·M·赫希(Steven M.Hersch)的医学博士申请的配套申请，题为肌酸安全、耐受性和有效性(CREST-E)。HD是一种常染色体显性、均匀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，另有150,000名健康的人被认为有患HD的直接风险。目前还没有有效的治疗方法来治疗HD，而HD的不断进展会导致残疾和死亡。来自HD小鼠模型和人类研究的证据表明，肌酸可能以一种剂量依赖的方式减缓HD的进程。有关血清和大脑的生物利用度、耐受性、HD体征和症状以及生物标记物的试点数据表明，每天30克肌酸是最佳剂量。 我们建议通过对650名有症状的HD患者进行随机、双盲、安慰剂对照、平行分组试验，每天服用30克肌酸来检验肌酸可以减缓HD下降的假设。主要结果变量将是从基线到36个月的总功能能力(TFC)评分的变化。这项研究将有96%的力量检测到临床上相关的25%的TFC减慢。这项试验将在亨廷顿研究小组(HSG)的主持下在全球约42个地点进行。 这个项目与NCCAM的使命是一致的，即通过科学的严格研究来探索替代疗法，如肌酸。这项研究具有重要的公共卫生影响。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，并将刺激对一系列相关神经退行性疾病的类似化合物的研究。此外，这项研究还将提供有关大剂量肌酸长期安全性的关键信息，大剂量肌酸被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。这将允许NCCAM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.