Neuroprotection Studies in PD: A Coordinating Center.

描述(由申请人提供)：美国国立卫生研究院帕金森氏病探索性试验(Net-PD)计划的建立是为了促进治疗方法的开发，以减缓这种慢性神经退行性疾病的进展。这个网络有效地执行了候选疗法的无效性研究，确定肌酸是一种具有治疗潜力的药物。随后设计了一项名为长期研究1(LS1)的第三阶段疗效试验，以评估肌酸在减缓帕金森病(PD)临床下降方面的疗效。LS1目前已开始运作，并成功地实现了招聘目标。参与者将被跟踪调查最短5年，最长8年。因此，最后的考察访问将在2014年6月至2015年5月之间进行。目前的申请要求通过完成NET-PD试验来开展临床协调中心的活动。这些活动以下列具体目标为指导。具体目标1是完成LS1中登记参与者的随访和增强保留率，以检验在多巴胺能治疗和最佳帕金森病护理的背景下，每天服用肌酸(10克/天)在减缓帕金森病临床下降方面比安慰剂更有效的基本假设。具体目标2是进行二次分析，以评估肌酸在基线和包括5-8年研究参与的最终随访之间的个别帕金森病临床措施上的有效性，以及对总体安全性和耐受性的分析。具体目标3是继续运作临床协调中心，以完成净PD研究，其中涉及(A)维持研究方案，(B)临床现场监督和培训，(C)维持质量和监管标准，(D)对临床地点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)关闭数据库并移交统计协调中心进行分析，(G)参与试验结果的分析计划、解释和报告，以及(H)协助统计协调中心将数据存档并存入公开数据库。具体目标4是维持一个允许与统计协调中心、临床站点、NINDS科学计划人员、NINDS数据和安全监测委员会以及NINDS监督委员会密切合作的行政结构。成功完成这些目标将实现Net-PD计划的目标，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的进展。

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.