Kinesia-D: Ambulatory PD Dyskinesia Monitor for Drug Therapy Titration

描述(申请人提供)：目标是开发和临床评估Kinesia-D“，这是一种无线、符合人体工程学的便携式运动障碍技术，旨在持续监测左旋多巴诱发的运动障碍(LID)和帕金森病(PD)的用药状态。使用多巴胺前体左旋多巴可以从药理上改善运动症状。虽然在帕金森病的治疗方面已经取得了重大进展，但平衡运动改善与治疗与慢性使用相关的运动障碍副作用(短暂、快速、不规则的运动)构成了一个关键的治疗挑战。大约30%的患者在治疗后5年内出现眼睑，10年后达到59%-100%。LID通过精疲力竭和疲劳、社交孤立和抑郁显著影响生活质量。随着盖子严重性的增加，医疗成本大幅上升。当将患有严重眼睑的PD患者与没有副作用的PD患者进行比较时，每年的费用增加了16,000美元以上。这一应用的价值是巨大的，因为现有的用于捕捉左旋多巴剂量反应的临床工具完全依赖于临床测试和/或患者对帕金森病震颤、运动障碍和全天自主运动的主观评估和区分能力。Kinesia-D不仅将对运动障碍和震颤严重程度进行客观而准确的评估，而且还将生成关于左旋多巴反应药物状态的报告：OFF(无PD症状改善)、ON(PD症状改善)和ON(运动障碍)。这一第二阶段的应用将开发一种系统，该系统可以全天连续评估运动障碍的严重程度，独立于日常生活活动，同时还允许舒适地穿戴，负担最小。这将与现有的震颤评分算法无缝集成，以同时评估PD症状的改善和LID的发生。这些分数将被用来确定运动障碍的严重程度和用药状态。报告将自动生成，并通过驻留在患者家中的支持宽带的平板电脑传输给临床医生，以指导左旋多巴治疗的滴定。一种可靠的检测和监测动态环境中运动障碍严重程度的方法，对于帮助临床医生优化患者用药方案，以及大规模制药行业开发新的PD药物和上市后监测都具有极高的价值。Kinesia-D将首先在一项家庭研究中得到验证，通过显示与患者运动障碍日记的高度相关性，然后使用Kinesia-D系统与传统方法比较治疗滴定患者的结果。临床结果的衡量将基于生活质量和运动评分的改善，以及在没有运动障碍的情况下服药状态下的时间增加。我们假设，商用Kinesia-D系统将持续量化日常生活活动中运动障碍的严重程度，通过平衡PD运动症状和对左旋多巴的运动障碍副作用反应来改善患者预后，并降低医疗保健和临床药物试验成本。

DESCRIPTION (provided by applicant): The objective is to develop and clinically assess Kinesia-D", a wireless, ergonomic, and portable movement disorder technology designed for continuous monitoring of levodopa-induced dyskinesia (LID) and medication state in Parkinson's disease (PD). Motor symptoms can be ameliorated pharmacologically with the dopamine precursor, levodopa. While significant strides have been made in the management of PD, balancing motor improvement with treatment dyskinesia side effects (brief, rapid, irregular movements) associated with chronic use poses a key therapeutic challenge. Approximately 30 percent of patients exhibit LID within 5 years of treatment and 59-100 percent by 10 years. LID significantly impact quality of life through exhaustion and fatigue, social isolation, and depression. Healthcare costs are substantially greater with increased LID severity. Yearly costs increase over $16,000 when comparing a PD patient with severe LID to one with no side effects. The value of this application is tremendous in that existing clinical tools for capturing he levodopa dose response are completely reliant on in-clinic testing and/or the patient's subjective assessment of and ability to distinguish between PD tremor, dyskinesias, and voluntary movements throughout the day. Kinesia-D will not only objectively and accurately rate dyskinesia and tremor severity on a continuous scale independent of each other and activities of daily living, but also generate reports on levodopa response medication states: OFF (no PD symptomatic improvement), ON (PD symptomatic improvement), and ON with dyskinesia. This Phase II application will develop a system which can continuously rate dyskinesia severity throughout the day independent of activities of daily living while also allowing comfortable wear with minimal burden. This will be seamlessly integrated with existing tremor scoring algorithms for simultaneous assessment of PD symptom improvement and LID occurrence. These scores will be used to determine dyskinesia severity and medication state. Reports will automatically be generated and transmitted to the clinician via a broadband-enabled tablet computer residing in the patient's home to guide titration of levodopa treatment. A reliable method for detecting and monitoring the severity of dyskinesia in an ambulatory setting would be highly valuable both for aiding clinicians in optimizing patient medication regimens and the massive pharmaceutical industry for developing new PD drugs and for post market surveillance. Kinesia-D will first be validated in a home study by showing high correlations to the patient dyskinesia diary and then be used to compare therapy titration patient outcome using the Kinesia-D system versus traditional methods. Clinical outcome measures will be based on improved quality of life and motor scores and increased hours in the ON medication state without dyskinesia. We hypothesize that the commercial Kinesia-D system will continuously quantify dyskinesia severity during activities of daily living, improve patient outcomes by balancing PD motor symptom and dyskinesia side effect response to levodopa, and reduce healthcare and clinical drug trial costs.