Tele-Health Extension for Phase 3 Parkinson's Disease Trial Cohorts

摘要 疾病修饰是帕金森病(PD)治疗中尚未得到满足的主要需求。目前临床 有希望的候选神经保护剂的试验受到重复输入的低效和不精确的限制。 自愿参与这些研究的帕金森氏症患者需要进行个人临床评估。 新兴的远程医疗和基于智能手机的远程传感器评估提供了帮助的机会 克服这些障碍，改善未来审判成功的前景。演示了 这些相对便宜的、可获得的用于测量PD进展的远程健康平台将 还要建立基础设施，以便在干预研究完成后对参与者进行长期跟踪。 STRATE-PD3和SURE-PD3是NINDS资助的潜在疾病修改的活跃的第三阶段试验 帕金森病的干预措施。这两项研究包括约600名早期帕金森病受试者，包括收集 DNA和连续血浆样本，以及子集连续多巴胺转运体(DAT)神经成像数据，将 成为帕金森氏病生物标记物计划(PDBP)的一部分。这项建议的目的是 利用现代技术开发、试点和实施100%虚拟模型以进行长期跟踪 利用远程医疗和智能手机平台对临床医生和患者报告进行量化监控 结果。具体目标(SA)1是为第三阶段试验的纵向远程跟踪建立基础设施 编队；a)从现场过渡到集中协调中心，以管理所有主题活动，b) 进行年度远程医疗研究访问(远程访问)计划，以及c)实施智能手机数据 为临床试验队列量身定做的收集平台。SA2将智能手机(患者驱动)与远程访问进行比较 (临床医生驱动的)结果：a)将这些平台的组件和组合特征以及它们的 多年来的变化，以及b)比较他们的能力：i)测量PD进展；ii)区分快慢 基于基线运动评分、DAT缺陷或血尿酸水平的进展者；以及iii)显示 伊拉地平或肌苷在各自试验中的持久性。SA3将探索新型智能手机-- 基于PD残疾及其进展的真实生活活动生物标记物，通常无法通过 传统的办公措施。被动收集关于移动和位置的智能手机数据的能力， 能够评估有意义地整合运动和非运动的体力活动和社交活动 我们将对其功能进行调查。该项目利用了NIH和Study的主要第三阶段试验投资 受试者通过延长他们的随访来建立远程健康指标在跟踪PD进展方面的效用 临床队列。预计其结果将加快对更多有希望的 疾病改良者的候选人。其结果将直接影响到合理选择 智能手机与远程访问监测在设计下一代帕金森病试验中的对比，并可能有助于识别和 证实帕金森病的新型数字和分子生物标记物。

Abstract Disease modification is the primary unmet need in Parkinson's disease (PD) therapeutics. Currently clinical trials of promising candidate neuroprotectants are limited by the inefficiency and imprecision of repeated in- person clinical assessments required of people with Parkinson's who volunteer to participate in these studies. Emerging telemedicine and smartphone-based remote sensor assessments provide opportunities to help overcome these obstacles and improve prospects for the success of future trials. Demonstrating the utility of these relatively inexpensive accessible tele-health platforms for the measurement of PD progression would also establish infrastructure for long-term follow up of participants after completion of interventional studies. STEADY-PD3 and SURE-PD3 are active NINDS-funded phase 3 trials of potential disease-modifying interventions in PD. Both studies, comprising ~600 early PD subjects, include biomarker sub-studies collecting DNA and serial plasma samples and in a subset serial dopamine transporter (DAT) neuroimaging data that will become part of the Parkinson's Disease Biomarker Program (PDBP). The objective of this proposal is to leverage modern technology to develop, pilot and implement a 100% virtual model for long-term follow up utilizing telemedicine and smartphone platforms for quantitative monitoring of clinician- and patient-reported outcomes. Specific Aim (SA) 1 is to establish infrastructure for longitudinal remote follow up of phase 3 trial cohorts; a) transitioning from site-based to a centralized coordination center to manage all subject activity, b) conducting an annual telemedicine research visit (tele-visit) program, and c) implementing a smartphone data collection platform tailored to a clinical trial cohort. SA2 is to compare smartphone (patient-driven) vs tele-visit (clinician-driven) outcomes by a) correlating these platforms' component and composite features, and their changes over years, and b) comparing their abilities to i) measure PD progression; ii) distinguish rapid vs slow progressors based on baseline motor scale scores, DAT deficit or serum urate levels; and iii) demonstrate persistence of any effects of isradipine or inosine in their respective trials. SA3 is to explore novel smartphone- based real-life mobility biomarkers of PD disability and its progression that are normally inaccessible with traditional office measures. The ability of passively collected smartphone data, on ambulation and location, to enable assessments of physical activity and socialization that meaningfully integrate motor and non-motor functions will be investigated. This project leverages the major phase 3 trial investments of NIH and study subjects by extending their follow up to establish the utility of tele-health metrics for tracking PD progression in clinical cohorts. Its results are expected to accelerate effective testing of a greater number of promising candidates for disease modification. The results will have an immediate impact on the rational selection of smartphone versus tele-visit monitoring in designing the next generation of PD trials, and may help identify and substantiate novel digital as well as molecular biomarkers of PD.