CYClical Lower Extremity exercise for Parkinsons trial (CYCLE Trial)

项目摘要/摘要 尽管治疗帕金森氏病(PD)的药物和手术方法取得了进展，但 有效的疾病修正治疗仍然难以捉摸。运动被认为是一种辅助治疗 疾病；然而，其疾病改变特性尚不清楚。数据表明，高强度运动有 改善帕金森病动物模型的神经保护特性和改善运动功能。我们前景看好的翻译 对人体的研究表明，有氧运动可以改善整体运动功能、上肢功能，以及 改变了中枢神经系统的激活模式。我们最近完成了一项100人随机临床试验。 试验，帕金森试验的周期性下肢锻炼(周期试验)(NIH R01NS673717)，结果 显示为期8周的高强度有氧运动计划显著提高了MDS-UPDRS III分数， 转弯和步态速度，以及信息处理。阳性结果一直持续到8周后 停止运动。这些积极的结果为评估长期政策的有效性提供了强有力的理由。 在以家庭为基础的环境中制定周期方案，努力影响更多的帕金森病患者。这个 该项目的主要目的是确定长期、高强度的有氧运动是否会改变疾病。 帕金森病患者的进展情况。提出了一种实用的随机临床试验方案。 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 大强度运动对帕金森病进展的影响。总而言之，从克利夫兰招募的250名PD患者 诊所和犹他大学将随机接受高强度的家庭锻炼或常规和常规护理 (UCC)组。循环试验方案将通过以下途径送到锻炼小组的家中 以消费者为基础的佩洛顿室内自行车，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 在注册时、3个月、6个月、9个月和12个月接受相同的运动和非运动评估方案。此外 对于临床测量，如MDS-UPDRS III，运动和非运动结果的系统量化 将使用PD性能测试(PD-PT)收集数据，PD-PT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控两组人的总体活动水平 传感器。结合临床和生物力学测量运动和认知能力将加速 对运动积极作用的潜在机制的调查和理解 疾病的发展。最后，运动表现数据包括心率、节奏和力量 将收集会话以监测锻炼依从性并建立锻炼反应预测模型。这个 模型将促进从一般建议到患者特定运动处方的过渡 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.