Kinesia-HS: High Sensitivity System for Facilitating Parkinson's Drug Trials

描述(由申请人提供)： 其目标是设计、构建和临床评估Kinesia-HS，这是一种促进针对帕金森氏病(PD)的神经保护干预措施的药物开发的综合解决方案。该系统将包括紧凑型患者佩戴的仪器和用于家庭监测的基于网络的基础设施，以在幅度和时间上显著提高运动症状的分辨率。已经有了巨大的增长和对神经保护治疗的积极研究，旨在减缓帕金森病的进展。治疗效果是通过患者症状随时间恶化的速度来判断的。目前评估帕金森氏病运动症状的标准是统一的帕金森病评定量表(UPDRS)，这是一种排名系统，临床医生必须在场才能提供主观整数评分来记录症状严重程度。UPDRS的离散性质使得它在神经保护药物研究中严重不足以衡量运动症状的恶化速度。这些药物针对的是早期帕金森病患者，当时症状几乎不明显。通常需要几年甚至几十年的时间，离散的UPDR才能检测到运动症状严重性的下降速度的显着变化。拟议系统的主要创新包括在临床研究中使用DBS来模拟疾病进展，使用高速视频作为直接链接到UPDRS进行敏感性验证的黄金标准，以及用于提高临床药物试验效率的标准化、基于网络的基础设施。我们将利用CleveMed之前开发的Kinesia系统，这是一种用于量化PD电机症状的紧凑型无线系统，其中包括用户可穿戴的运动传感器和用于自动对患者进行检查的交互式软件。在两项大型临床研究中，运动传感技术成功地证明了PD运动症状的客观量化与临床UPDRS运动评分高度相关。虽然以前的现有技术将被用来加速开发并增加项目成功的可能性，但制药应用程序需要重要的新颖软件开发、系统集成和评估。为了验证症状严重程度的微小变化的量化，现有的量化震颤和运动迟缓严重程度的算法将与高速、校准的视频进行测试，这些视频提供了准确的手部运动测量。除了在家中监测帕金森病症状的高灵敏度仪器外，拟议系统的一个主要创新是基础设施主干，使Kinesia-HS输出能够直接集成到目前临床试验中使用的标准化电子数据捕获软件中。与传统方法相比，这个客观家庭评估的标准化平台可以更快地产生临床显著结果，并具有更高的分辨率，从而使突破性疗法能够更快地推向市场，并降低开发成本。 公共卫生相关性： 制药公司非常重视旨在减缓帕金森氏症进展的神经保护剂。目前评估运动症状对治疗的反应的标准是一个主观的、完整的评分表，它不能提供必要的分辨率来衡量疾病进展过程中运动症状的变化速度。拟议的系统将包括紧凑型患者佩戴的仪器和基于网络的家庭监测基础设施，以显著提高幅度和时间上的运动症状解决能力，并易于整合到临床药物试验中，以加快帕金森病干预措施的开发。

DESCRIPTION (provided by applicant): The objective is to design, build, and clinically assess Kinesia-HS, an integrated solution to facilitate pharmaceutical development of neuroprotective interventions targeted to Parkinson's disease (PD). The system will include both compact patient-worn instrumentation and web-based infrastructure for home monitoring to provide significantly increased motor symptom resolution in both amplitude and time. There has been tremendous growth and active research into neuroprotective treatments designed to slow the progression PD. Treatment efficacy is judged by the rate at which patient symptoms deteriorate over time. The current standard in evaluating PD motor symptoms is the Unified Parkinson's Disease Rating Scale (UPDRS), a ranking system in which clinicians must be present to provide a subjective integer score to document symptom severity. The discrete nature of the UPDRS renders it profoundly inadequate for measuring the rate of deterioration of motor symptoms in a neuroprotective drug study. These drugs target patients with early PD, when symptoms are barely noticeable. It often takes years or even decades before the discrete UPDRS can detect a significant change in the rate of decline of motor symptom severity. The primary innovations of the proposed system include utilizing DBS in a clinical study to simulate disease progression, using high speed video as the gold standard linked directly back to the UPDRS for sensitivity validation, and a standardized, web-based infrastructure to improve the efficiency of clinical drug trials. We will leverage CleveMed's previously developed Kinesia system, a compact wireless system to quantify PD motor symptoms, which includes user worn motion sensors and interactive software to automate a patient exam. In two large clinical studies, the motion sensing technology successfully demonstrated objective quantification of PD motor symptoms with high correlations to clinical UPDRS motor scores. While previously existing technology will be leveraged to speed development and increase likelihood of project success, significant novel software development, system integration, and evaluation is required for the pharmaceutical application. In order to validate the quantification of very slight changes in symptom severity, the existing algorithms for quantifying tremor and bradykinesia severities will be tested against high-speed, calibrated videos that give precise measures of hand movements. In addition to highly sensitive instrumentation for monitoring PD symptoms in the home, a primary innovation of the proposed system is the infrastructure backbone to enable the straightforward integration of Kinesia-HS outputs into standardized electronic data capture software currently used in clinical trials. This standardized platform for objective home assessments could lead to clinically significant results faster and with improved resolution compared to traditional methods, which could enable breakthrough therapies to get to market faster and lower developmental costs. PUBLIC HEALTH RELEVANCE: Pharmaceutical companies are placing great emphasis on neuroprotective agents designed to slow the progression of Parkinson's disease. The current standard for evaluating motor symptoms in response to therapy is a subjective, integer rating scale that does not provide the resolution necessary to measure the rate at which motor symptoms change during disease progression. The proposed system will include both compact patient-worn instrumentation and web-based infrastructure for home monitoring to provide significantly increased motor symptom resolution in both amplitude and time and easy integration into clinical drug trials to speed the development of PD interventions.