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

Kinesia-HS：促进帕金森病药物试验的高灵敏度系统

• 批准号: 8200116
• 负责人: Dustin A. Heldman
• 金额: $ 25.6万
• 依托单位: GREAT LAKES NEUROTECHNOLOGIES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8200116
• 关键词: Algorithms; Back; Bradykinesia; Clinical; Clinical Data; Clinical Research; Clinical Trials; Complex; Computer software; Data; Data Analyses; Data Collection; Data Storage and Retrieval; Databases; Deep Brain Stimulation; Deterioration; Development; Disease Progression; Drug Delivery Systems; Evaluation; Fingers; Gold; Growth; Hand; Home environment; Intervention; Lead; Link; Marketing; Measures; Methods; Monitor; Motion; Motor; Movement; Movement Disorders; Nature; Neuroprotective Agents; Online Systems; Outcome; Outcome Measure; Output; Parkinson Disease; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Protocols documentation; Quality of life; Reporting; Research; Research Infrastructure; Resolution; Severities; Simulate; Site; Solutions; Speed; Symptoms; System; Systems Integration; Tablets; Technology; Testing; Time; Treatment Efficacy; Tremor; Validation; Vertebral column; Video Recording; Visit; Wireless Technology; Work; clinically significant; commercialization; cost; design; diaries; electronic data; functional disability; improved; innovation; instrumentation; motion sensitivity; novel; prototype; response; sensor; software development; success; therapy design; tool; touchscreen; voltage; web interface

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.

描述（由申请人提供）： 目的是设计，构建和临床评估Kinesia-HS，这是一种综合解决方案，旨在促进针对帕金森病（PD）的神经保护干预措施的药物开发。该系统将包括紧凑型患者佩戴仪器和基于网络的家庭监测基础设施，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积极的研究，旨在减缓进展PD的神经保护治疗。治疗效果通过患者症状随时间恶化的速率来判断。目前评估PD运动症状的标准是统一帕金森病评定量表（Unified Parkinson's Disease Rating Scale，简称PDRS），这是一种排名系统，临床医生必须在场，以提供主观整数评分来记录症状严重程度。在神经保护性药物研究中，运动症状评分的离散性使得它完全不足以测量运动症状的恶化率。这些药物针对早期PD患者，当症状几乎不明显时。通常需要数年甚至数十年的时间，离散的运动症状评分系统才能检测到运动症状严重程度下降率的显著变化。拟议系统的主要创新包括在临床研究中利用DBS模拟疾病进展，使用高速视频作为直接连接到ADRS的金标准进行灵敏度验证，以及标准化的基于网络的基础设施，以提高临床药物试验的效率。我们将利用CleveMed先前开发的Kinesia系统，一个紧凑的无线系统，以量化PD运动症状，其中包括用户佩戴的运动传感器和交互式软件，以自动化患者exam. In两个大型临床研究，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的运动评分高度相关。虽然将利用现有技术来加快开发速度并增加项目成功的可能性，但制药应用需要大量的新软件开发、系统集成和评估。为了验证症状严重程度非常轻微的变化的量化，将对用于量化震颤和运动迟缓严重程度的现有算法进行测试，这些算法将针对能够精确测量手部运动的高速校准视频进行测试。除了用于在家中监测PD症状的高灵敏度仪器外，所提出的系统的主要创新是基础设施骨干，以使Kinesia-HS输出能够直接集成到目前用于临床试验的标准化电子数据采集软件中。与传统方法相比，这种用于客观家庭评估的标准化平台可以更快地获得具有临床意义的结果，并具有更高的分辨率，这可以使突破性疗法更快地进入市场并降低开发成本。 公共卫生关系： 制药公司非常重视旨在减缓帕金森病进展的神经保护剂。目前用于评价运动症状对治疗的反应的标准是主观的整数评定量表，其不提供测量疾病进展期间运动症状变化速率所需的分辨率。拟议的系统将包括紧凑的患者佩戴仪器和基于网络的家庭监测基础设施，以在幅度和时间上显着提高运动症状的分辨率，并易于集成到临床药物试验中，以加快PD干预措施的开发。