CYClical Lower Extremity exercise for Parkinsons trial (CYCLE Trial)

项目概要/摘要 尽管帕金森病（PD）治疗的药物和手术方法取得了进展，但 有效的疾病改善治疗仍然是难以捉摸的。运动被认为是治疗肥胖的一种有效方法。 疾病;然而，其改变疾病的特性尚不清楚。数据显示，高强度运动 在PD动物模型中具有神经保护特性并改善运动功能。我们的翻译 人体研究表明，有氧运动可改善整体运动功能、上肢表现， 中枢神经系统激活模式的改变我们最近完成了一项100人的随机临床试验， 试验，周期性降低帕金森试验（周期试验）（NIH R 01 NS 673717），和结果 表明8周的高强度有氧运动计划显著改善了MDS-GRS III评分， 转弯和步态速度，以及信息处理。阳性结果持续了8周， 运动停止。这些积极的结果提供了强有力的理由，以评估长期的有效性， 在家庭环境中实施CYCLE方案，以影响更多的PD患者。的 该项目的主要目的是确定长期高强度有氧运动是否能改变疾病 PD患者的进展。提出了一项实用的随机临床试验， 评估将与运动和非运动性能的生物力学测量相结合，以确定 高强度运动对PD进展的影响。总之，从克利夫兰招募了250名PD患者， 诊所和犹他州大学将被随机分配到高强度家庭锻炼或常规和常规护理 (UCC)组CYCLE试验方案将通过 基于消费者的Peloton室内自行车，参与者将被指示每周锻炼3次，持续12个月; UCC小组将被指示从事他们的正常活动。运动组和对照组将 在入组、3、6、9和12个月时接受相同的运动和非运动评价方案。此外 到临床测量，如MDS-GRS III，运动和非运动结局的系统量化 将使用PD性能测试（PD-PT）收集，这是一套经过验证的基于生物力学的iPad 在艾伯茨博士的实验室里创建的应用程序。将通过可穿戴设备监测两组的总体活动水平 传感器.结合运动和认知表现的临床和生物力学测量， 调查和了解潜在的机制，运动的积极影响， 疾病进展。最后，运动性能数据，包括心率，节奏和功率，从每个 会议将被收集，以监测运动依从性，并建立运动反应预测模型。的 模型将促进从一般建议过渡到患者特定的运动处方， 哪些潜在的结果是可以估计的。

PROJECT SUMMARY/ABSTRACT Despite advances in pharmaceutical and surgical approaches to the treatment of Parkinson’s disease (PD), an effective disease modifying treatment remains elusive. Exercise is accepted as an adjunctive treatment to the disease; however, its disease altering properties are unclear. Data indicate that high intensity exercise has neuroprotective properties and improves motor functioning in animal models of PD. Our promising translational work in humans indicated aerobic exercise improves global motor function, upper extremity performance, and altered patterns of central nervous system activation. We recently completed a 100 person randomized clinical trial, CYClical Lower Extremity exercise for Parkinson’s trial (CYCLE Trial) (NIH R01NS673717), and results indicated an 8-week high intensity aerobic exercise program significantly improved MDS-UPDRS III scores, turning and gait speed, and information processing. The positive results persisted up to eight weeks after exercise cessation. These positive results provide strong rationale to evaluate the effectiveness of a long-term CYCLE protocol in a home-based setting in an effort to impact a greater number of individuals with PD. The primary aim of this project is to determine if long-term, high intensity aerobic exercise alters disease progression in individuals with PD. A pragmatic randomized clinical trial is proposed in which blinded clinical assessments will be coupled with biomechanical measures of motor and non-motor performance to determine the impact of high-intensity exercise on PD progression. In sum, 250 PD patients recruited from the Cleveland Clinic and University of Utah will be randomized to a high-intensity home exercise or usual and customary care (UCC) group. The CYCLE Trial protocol will be delivered to the home of the exercise group through the consumer-based Peloton Indoor Cycle, and participants will be instructed to exercise 3x/week for 12 months; the UCC group will be instructed to engage in their normal activities. The exercise and control groups will undergo identical motor and non-motor evaluation protocols at enrollment, 3, 6, 9, and 12 months. In addition to clinical measures such as the MDS-UPDRS III, systematic quantification of motor and non-motor outcomes will be collected using the PD-Performance Test (PD-PT), a validated set of biomechanical-based iPad applications created in Dr. Alberts’ lab. Overall activity levels will be monitored for both groups via a wearable sensor. Combining clinical and biomechanical measures of motor and cognitive performance will accelerate the investigation and understanding of potential mechanisms underlying the positive effects of exercise on disease progression. Finally, exercise performance data including heart rate, cadence and power from each session will be gathered to monitor exercise compliance and build an exercise response predictive model. The model will facilitate a transition from general recommendation to a patient-specific exercise prescription in which potential outcomes can be estimated.