Coordination and Statistics for CoQ10 in HD [2CARE]

描述（由申请人提供）：本申请要求为辅酶Q10（CoQ）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Merit E的配套应用程序。Cudkowicz，医学博士来自马萨诸塞州总医院的标题为“亨廷顿病中的辅酶Q10（2CARE）。该项目的主要目的是进行一项多中心、随机、双盲、安慰剂对照的试验，剂量为2400 mg/天，涉及1100名非卧床HD受试者，前瞻性随访5年。辅酶Q是一种参与线粒体电子转移的辅因子和一种抗氧化剂，已证明HD转基因小鼠模型的存活率增加，并在HD和帕金森病的人体试验中取得了有希望的结果。据推测，高剂量辅酶Q的长期治疗将减缓HD的进行性功能下降。我们申请的具体目的是（1）为试验提供项目协调，包括：开发和实施基于网络的随机化和入组程序，提供研究文件（方案、知情同意书和同意书范本、操作手册、病例报告表）、培训研究中心工作人员和标准化研究程序、促进招募和保留不同的研究受试者样本，以及研究药物的包装和分发;（2）为试验提供数据管理，包括：接收并将所有数据输入关系数据库，生成并解决数据查询，监测重要研究事件，以及维护合规和安全的数据环境;以及（3）为试验提供生物统计学支持，包括：完善和实施统计分析计划，以实现试验的特定目标;设计和实施中期监查计划，允许根据以下任一情况的早期证据修改或终止研究：（i）安全性问题，（ii）与NINDS指定的数据和安全性监测委员会（DSMB）一起提供压倒性的有效性证据或（iii）无效性证据;并为DSMB编写公开和非公开会议报告。

DESCRIPTION (provided by applicant): This application requests funding for the study coordination, data management, and biostatistical support for a Phase III clinical trial of Coenzyme Q10 (CoQ) in Huntington's disease (HD). This is a companion application to that of Merit E. Cudkowicz, M.D. from Massachusetts General Hospital entitled "Coenzyme Q10 in Huntington's Disease (2CARE)." The primary aim of the project is to conduct a multicenter randomized, double-blind, placebo-controlled trial of CoQ at a dosage of 2400 mg/day involving 1100 ambulatory subjects with HD followed prospectively for 5 years. CoQ is a cofactor involved in mitochondrial electron transfer and an antioxidant that has demonstrated increased survival in a transgenic mouse model of HD and promising results in human trials in HD and Parkinson's disease. It is hypothesized that chronic treatment with high-dosage CoQ will slow the progressive functional decline in HD. The specific aims of our application are (1) To provide project coordination for the trial including: development and implementation of web-based randomization and enrollment procedures, provision of study documents (protocol, model consent and assent forms, operations manual, case report forms), training of site personnel and standardization of study procedures, facilitation of recruitment and retention of a diverse sample of research subjects, and packaging and distribution of study drug; (2) To provide data management for the trial including: receipt and entry of all data in a relational database, generation and resolution of data queries, monitoring of important study events, and maintenance of a compliant and secure data environment; and (3) To provide biostatistical support for the trial including: refinement and implementation of the statistical analysis plan to address the specific aims of the trial; design and implementation of an interim monitoring plan that will allow modification or termination of the study on the basis of early evidence of either (i) safety concerns, (ii) overwhelming evidence of efficacy, or (iii) futility, in conjunction with the NINDS-appointed Data and Safety Monitoring Board (DSMB); and preparation of open- and closed-session reports for the DSMB.