Neuroprotection Studies in PD: A Coordinating Center.

描述（由申请人提供）：建立NIH帕金森病探索性试验（NET-PD）计划，以促进开发减缓这种慢性神经退行性疾病进展的疗法。该网络有效地执行了候选疗法的无效研究，该研究将肌酸确定为具有治疗潜力。随后的3期疗效试验，称为长期研究1（LS 1），正在设计和执行，以评估肌酸在减缓帕金森病（PD）临床下降的疗效。LS 1目前正在运作，并已成功实现征聘目标。参与者将被随访至少5年，最长8年。因此，最终研究访视将在2014年6月至2015年5月之间进行。目前的申请要求资金通过完成NET-PD试验开展临床协调中心活动。这些活动遵循以下具体目标。具体目标1是完成随访并提高LS 1中入组受试者的保留率，以检验主要假设，即在多巴胺能治疗和最佳PD护理的背景下，肌酸每日给药（10 gm/天）在减缓PD临床下降方面比安慰剂更有效。具体目的2是进行次要分析，以评价基线和最终随访访视（包括5-8年研究参与）之间肌酸对个体PD临床指标的疗效，以及总体安全性和耐受性分析。具体目标3是继续运营临床协调中心，以完成NET-PD研究，包括（a）维护研究方案，（B）临床研究中心监督和培训，（c）维护质量和监管标准，（d）对临床研究中心的实验治疗分配进行后勤监督，（e）接收和管理所有临床试验数据，（f）关闭数据库并将其转移至统计协调中心进行分析，（g）参与分析计划、解释和报告试验结果，以及（h）协助统计协调中心在公开数据库中记录和存档数据。具体目标4是维持一个允许与统计协调中心、临床研究中心、NINDS科学项目人员、NINDS数据和安全性监查委员会以及NINDS监督委员会密切合作的管理结构。成功完成这些目标将实现NET-PD项目的目标，即建立一个创新的、以证据为基础的过程，通过该过程选择和测试潜在的治疗方法以减缓PD进展。

DESCRIPTION (provided by applicant): The NIH Exploratory Trials in Parkinson's Disease (NET-PD) program was established to facilitate the development of therapies to slow the progression of this chronic neurodegenerative disease. This network effectively executed futility studies of candidate therapies, which identified creatine as a having therapeutic potential. A subsequent Phase 3 efficacy trial, known as Long-term Study 1 (LS1) was designed and is being executed to evaluate the efficacy of creatine in slowing clinical decline in Parkinson's Disease (PD). LS1 is currently operational and has successfully met recruitment goals. Participants are being followed for a minimum of 5 years and maximum of 8 years. As a result, the final study visits will occur between June 2014 and May 2015. The current application requests funds to carry out Clinical Coordination Center activities through the completion of the NET-PD trials. These activities are guided by the following specific aims. Specific Aim 1 is to complete follow-up and enhance retention of enrolled participants in LS1 in order to test the primary hypothesis that daily administration of creatine (10gm/day) is more effective than placebo in slowing clinical decline in PD against the background of dopaminergic therapy and best PD care. Specific Aim 2 is to perform secondary analyses to evaluate the efficacy of creatine on individual PD clinical measures between baseline and the final follow-up visit that encompasses 5-8 years of study participation, as well as analyses of overall safety and tolerability. Specific Aim 3 is to continue to operate a Clinical Coordination Center for the completion of NET-PD studies, which involves (a) maintenance of study protocols, (b) Clinical Site oversight and training, (c) maintenance of quality and regulatory standards, (d) logistical oversight of experimental treatment distribution to Clinical Sites, (e) receipt and management of all clinical trial data, (f) close out the database and transfer to the Statistical Coordination Ceter for analysis, (g) participation in the analysis plans, interpretation and reporting of the trial reults, and (h) assisting the Statistical Coordinating Center in documenting and archiving the data in a publicly available database. Specific Aim 4 is to maintain an administrative structure that allows close collaboration with the Statistical Coordination Center, the Clinical Sites, NINDS Scientific Program personnel, the NINDS Data and Safety Monitoring Board and the NINDS Oversight Committee. Successful completion of these aims will achieve the goal of the NET-PD program to establish an innovative, evidence-based process by which potential therapies are selected and tested for slowing of PD progression.