Coordination and Statistics for CoQ10 in HD [2CARE]

该申请要求为研究协调、数据管理和生物统计支持提供资金， 辅酶Qio（CoQ）治疗亨廷顿病（HD）的III期临床试验。这是一个伴侣 适用于Merit E。Cudkowicz，医学博士来自马萨诸塞州总医院的名为“辅酶 Qio在亨廷顿病中的作用（2CARE）。“该项目的主要目的是进行多中心 一项随机、双盲、安慰剂对照试验，剂量为2400 mg/天，涉及1100名 前瞻性随访非卧床HD受试者5年。CoQ是参与以下过程的辅助因子 线粒体电子转移和抗氧化剂，已经证明增加了转基因动物的存活率。 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的慢性治疗将减缓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）、研究中心培训 人员和标准化的研究程序，促进招聘和留住不同的 研究受试者样本、研究药物的包装和分发;（2）提供数据管理 包括：接收和输入关系数据库中的所有数据，生成和解析数据 查询、监测重要的研究事件以及维护合规和安全的数据环境; 及（3）为试验提供生物统计支援，包括： 统计分析计划，以解决试验的具体目标;设计和实施临时 允许根据早期证据修改或终止研究的监查计划 （i）安全性问题，（ii）压倒性的疗效证据，或（iii）无效，与 NINDS任命的数据和安全监测委员会（DSMB）;以及公开和非公开会议的准备 DSMB的报告。

This application requests funding for the study coordination, data management, and biostatistical support for a Phase III clinical trial of Coenzyme Qio (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 Qio 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 five 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.