The Cyclical Lower-extremity Exercise for Parkinson's Trial

描述（由申请人提供）：目前的医疗和手术方法是昂贵的，并与各种可能损害患者生活质量的副作用有关。开发一种非药物、非手术治疗方法来改善运动功能，将为目前的PD治疗方法提供一种有吸引力的辅助手段。动物研究表明，强迫运动可以改善运动功能，并具有神经保护作用。我们假设，人类和动物实验之间的明显矛盾的结果是在使用的运动模式的差异的结果。人体实验采用自愿的方式，而动物实验则采用强迫的方式. PD模型为PD患者使用强迫运动干预提供了理论框架和依据。根据动物研究，运动激活减少可能会限制PD患者以必要的速率产生自主运动的能力，以改善整体运动功能。我们开发了一种安全的下肢强制运动范式，以增加PD患者的自主运动，帮助他们安全地实现高于自主运动率的运动率。我们的R21项目的结果表明，完成8周强制运动干预的患者临床运动评分改善了25%，而完成类似有氧强度的自愿运动干预的患者临床评分没有改善。我们最近的功能磁共振成像数据表明，强迫运动在帕金森病患者产生类似的皮质下和皮质的激活模式，是看到管理后的左旋多巴。运动功能的整体改善和神经活动的增加表明，强迫运动可能会改变PD患者的脑功能。本项目的目的是确定和比较强迫与自愿运动对PD运动和非运动功能的影响以及神经活动模式的相关变化。我们拟进行一项单中心、平行组、病例对照、评分者盲法研究。该项目将是我们在人类PD患者中使用临床和客观生物力学结果直接比较强迫和自愿运动对运动和非运动功能的影响的努力的继续。共100例轻度至中度特发性PD患者将随机分配至自愿、强迫或无运动对照组。将在5个时间点进行临床和生物力学评估：基线、治疗中期、治疗结束（EOT）、EOT + 4和EOT + 8周。据推测，与自愿和不运动组相比，完成强制运动的患者将表现出运动功能的全面改善和非运动症状的减少。如果强迫运动被证明是有效的，它可能成为一个可行的替代或辅助治疗药物或手术方法。建议的自行车干预是简单的，可以自我指导，是相对便宜的（〜 2,500美元的消费者版本），并可以立即转化为住院或门诊临床设置或病人的家。

DESCRIPTION (provided by applicant): Current medical and surgical approaches are expensive and are associated with a variety of side effects that may compromise the patient's quality of life. The development of a non-drug, non-surgical therapeutic approach to improve motor function would provide an attractive adjunct to current PD treatment approaches. Animal studies have shown that forced-exercise improves motor function and has neuroprotective qualities. We hypothesize that the apparent contradictory results between human and animal experiments is the result of differences in the exercise paradigms used. The human experiments utilized voluntary whereas forced- exercise was used in animals. Models of PD provide a theoretical framework and rationale for the use of a forced-exercise intervention for PD patients. Decreased motor activation may limit PD patients' ability to generate voluntary movements at rates necessary, based on animal studies, to improve global motor functioning. We developed a safe lower extremity forced-exercise paradigm to augment the voluntary movements of PD patients to assist them in safely achieving an exercise rate greater than their voluntary rate. The results of our R21 project indicate that patients completing an 8-week forced-exercise intervention exhibit a 25% improvement in clinical motor rating scores whereas patients completing a voluntary exercise intervention, of similar aerobic intensity, exhibited no improvements in clinical ratings. Our recent fMRI data indicate that forced-exercise in PD patients produces a similar subcortical and cortical pattern of activation as is seen following administration of levodopa. Global improvements in motor function and increased neural activity suggest forced-exercise may be altering brain function in PD patients. The goal of this project is to determine and compare the effects of forced versus voluntary exercise on PD motor and non-motor function and associated changes in the pattern of neural activity. We propose to conduct a single-center, parallel-group, case-controlled, rater-blinded study. This project will be a continuation of our effort to directly compare the effects of forced and voluntary exercise on motor and non-motor function using clinical and objective biomechanical outcomes in human PD patients. A total of 100 mild to moderate idiopathic PD patients will be randomized to a voluntary, forced or no-exercise control group. Clinical and biomechanical assessments will be performed at five time points: Baseline, mid-treatment, end of treatment (EOT), EOT + 4 and EOT + 8 weeks. It is hypothesized that patients completing forced-exercise will exhibit a global improvement in motor function and reduced non-motor symptoms compared to the voluntary and no-exercise groups. If forced- exercise is shown effective, it could become a viable alternative or adjunct therapy to pharmacologic or surgical approaches. The proposed cycling intervention is simple, can be self-directed, is relatively inexpensive (~$2,500 for a consumer version) and could immediately be translated to an inpatient or outpatient clinical setting or a patient's home.