NIH Exploratory Trials in Parkinson's Disease (NET-PD): Clinical Site

描述（由申请人提供）：帕金森病（PD）是最常见的成人神经退行性疾病之一，在北美和欧盟影响超过100万人。虽然目前可用的药物治疗可以获得短暂的症状改善，但功能能力会随着时间的推移而恶化。开发可以减缓或阻止PD进展的疗法将填补这些患者的主要未满足的医疗需求。作为确定此类疗法的第一步，NINDS帕金森病探索性试验（NET-PD）网络成功完成了无效研究，该研究将肌酸确定为减缓PD临床下降的潜在药物。NET-PD网络目前正在进行一项大型的长期研究。3期试验（称为LS 1）比较肌酸与安慰剂。我们的网站自成立以来一直是NET-PD网络的一部分，我们参加了所有的NET-PD活动。我们的研究中心是由托马斯杰斐逊大学和兰克瑙医学中心的研究中心组成的联盟，已入组50例受试者进入LS 1研究（所有LS 1研究中心中入组人数最多的7例），并且具有良好的受试者保留和随访记录。在当前申请涵盖的更新期内，建议继续和完成LS 1研究的以下具体目标：目的1保留当前受试者并完成对入组受试者的随访，以检验每日给予肌酸在多巴胺能治疗和最佳PD护理的背景下，在减缓基线和5年随访访视之间PD的临床下降方面，（10 gm/天）比安慰剂更有效;目的2进行次要疗效分析，以评估肌酸对参与研究5-8年期间收集的个体PD临床指标的影响，以及总体安全性和耐受性分析;目的3帕金森病认知结局量表的应用范围（SCOPA-COG）对检测相对早期的PD患者队列中的认知变化敏感，将沿着该组合的敏感性或评估PD患者的纵向变化。PI将与统计协调中心和认知写作小组（他一直是该小组的负责人）合作，以实现这一目标。此外，我们将使用人口统计学、伴随用药和基线时的共病信息以及沿着SCOPA-COG和符号数字模态测试（SDMT）（LS 1中认知功能的主要测试）的测量结果，分析和撰写研究早期经治PD中认知功能潜在临床预测因素的手稿。 相关性（见说明）：PD导致的累积残疾是生活质量下降和医疗保健费用增加的主要来源。尽管我们对PD的病理生理学的理解取得了进展，但目前还没有减缓不可阻挡的临床下降的治疗方法。LSI将有助于确定肌酸是否可以减缓临床衰退，并提供比目前更好的早期PD病程信息。 免责声明：请注意，以下评论是由审查员在研究部分会议之前准备的，并且以基本上未经编辑的形式提供。 虽然审查人员有机会根据小组讨论情况更新或修订其书面评价，但不能保证在会议讨论之后更新了个人评论。 因此，这些评论可能并不完全反映小组讨论结束时个人评论员的最终意见或小组的最终多数意见。因此，讨论的简历和摘要是评审员在会议上实际认为关键的最后一句话。

DESCRIPTION (provided by applicant): Parkinson's disease (PD) is one of the most common adult neurodegenerative disorders, affecting over 1 million people in North America and the European Union. Although transient symptomatic improvement can be obtained with currently available pharmacotherapies, functional ability deteriorates over time. Development of therapies that can slow or forestall the progression of PD would fill a major unmet medical need of these patients. As a first step in identifying such therapies, the NINDS Exploratory Trials in Parkinson's disease (NET-PD) network successfully completed futility studies, which identified creatine as a potential agent to slow clinical decline in PD. The NET-PD network is now conducting a large, long-term. Phase 3 trial (known as LS1) comparing creatine to placebo. Our site has been part of the NET-PD network since its inception and we have participated in all of the NET-PD activities. Our site, a consortium of sites at Thomas Jefferson University and at Lankenau Medical Center, has enrolled 50 subjects into the LS1 study (7"' highest enrollment of all LS1 sites) and has an excellent record or subject retention and follow-up. During the renewal period covered in the current application, the following specific aims for continuation and completion of the LS1 study, are proposed: Aim 1 Retain current subjects and complete follow-up and of enrolled participants in order to test the primary hypothesis that daily administration o creatine (10gm/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5 year follow-up visit, against the background of dopaminergic therapy and best PD care; Aim 2 Perform secondary efficacy analyses to evaluate the effect of creatine on individual PD clinical measures collected over the 5-8 years of study participation, as well as analyses of overall safety and tolerability; Aim 3 The extent to which the scales for Outcomes of Parkinson's disease-cognition (SCOPA-COG) is sensitive to detect cognitive changes in a relatively early cohort of PD patients will be examined along with the sensitivity of this battery or assessing longitudinal changes in PD patients. The PI will work with the Statistical Coordination Center and the Cognition Writing Group (of which he has been the head) to achieve this aim. In addition, we will contribute to the analysis and writing of a manuscript examining potential clinical predictors of cognitive function in early, treated PD, using demographic, concomitant medication, and comorbid disease information at baseline along with measurements from the SCOPA-COG and Symbol Digit Modalities Test (SDMT), the principal tests of cognitive function in LS1. RELEVANCE (See Instructions): The accumulated disability that PD causes is a major source of diminished quality of life and increased health care costs. Despite the advances in our understanding of the pathophysiology in PD, there are no current therapies that slow the inexorable clinical decline. LSI will help to determine if creatine can slow clinical decline and provide better information on the course of early PD than is currently available. Disclaimer: Please note that the following critiques were prepared by the reviewers prior to the Study Section meeting and are provided in an essentially unedited form. While there is opportunity for the reviewers to update or revise their written evaluation, based upon the group's discussion, there is no guarantee that individual critiques have been updated subsequent to the discussion at the meeting. Therefore, the critiques may not fully reflect the final opinions of th individual reviewers at the close of group discussion or the final majority opinion of the group. Thus the Resume and Summary of Discussion is the final word on what the reviewers actually considered critical at the meeting.