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

描述（由申请人提供）：目的是开发和临床评估Kinesia-D”，这是一种无线、人体工程学和便携式运动障碍技术，旨在连续监测帕金森病（PD）中左旋多巴诱导的运动障碍（LID）和药物状态。运动症状可以通过多巴胺前体左旋多巴来改善。虽然在PD管理方面取得了重大进展，但平衡运动改善与长期使用相关的治疗运动障碍副作用（短暂、快速、不规则运动）构成了关键的治疗挑战。大约30%的患者在治疗5年内表现出LID，10年内表现出59- 100%。LID通过疲惫和疲劳，社会孤立和抑郁显着影响生活质量。随着LID严重程度的增加，医疗保健成本大幅增加。当将患有严重LID的PD患者与没有副作用的患者进行比较时，每年的费用增加超过16，000美元。该应用的价值是巨大的，因为用于捕获左旋多巴剂量反应的现有临床工具完全依赖于临床测试和/或患者对PD震颤、运动障碍和全天自主运动的主观评估和区分PD震颤、运动障碍和自主运动的能力。Kinesia-D不仅可以在独立于彼此和日常生活活动的连续量表上客观准确地评定运动障碍和震颤严重程度，而且还可以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伴运动障碍。该II期申请将开发一种系统，该系统可以在一天中连续评估运动障碍的严重程度，而不受日常生活活动的影响，同时还可以以最小的负担舒适地佩戴。这将与现有的震颤评分算法无缝集成，以同时评估PD症状改善和LID发生。这些评分将用于确定运动障碍的严重程度和药物状态。报告将自动生成并通过患者家中的宽带平板电脑传输给临床医生，以指导左旋多巴治疗的滴定。在门诊环境中检测和监测运动障碍严重程度的可靠方法对于帮助临床医生优化患者药物治疗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非常有价值。Kinesia-D将首先在家庭研究中通过显示与患者运动障碍日记的高度相关性进行验证，然后用于比较使用Kinesia-D系统与传统方法的治疗滴定患者结局。临床结局指标将基于生活质量和运动评分的改善以及无运动障碍的ON药物状态时间的增加。我们假设，商业Kinesia-D系统将在日常生活活动中持续量化运动障碍的严重程度，通过平衡PD运动症状和运动障碍对左旋多巴的副作用反应来改善患者结局，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.