The Cyclical Lower-extremity Exercise for Parkinson's Trial

描述(由申请人提供)：目前的内科和外科治疗方法费用昂贵，且与各种副作用相关，这些副作用可能会危及患者的生活质量。开发一种非药物、非手术的治疗方法来改善运动功能将为目前的帕金森病治疗方法提供一个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结果是所使用的运动范例不同的结果。人体实验使用的是自愿运动，而强迫运动则是在动物身上进行的。帕金森病的模型为对帕金森病患者使用强制运动干预提供了理论框架和理论基础。根据动物研究，运动激活减少可能会限制帕金森病患者以改善全球运动功能所需的速度产生自愿运动的能力。我们开发了一种安全的下肢强迫运动范例，以增加PD患者的自愿活动，以帮助他们安全地实现高于其自愿运动率的运动率。我们R21项目的结果表明，完成8周强迫运动干预的患者在临床运动评级方面表现出25%的改善，而完成自愿运动干预、具有类似有氧强度的患者在临床评级方面没有改善。我们最近的fMRI数据表明，PD患者的强迫运动产生了类似于左旋多巴注射后的皮质下和皮质下的激活模式。全球运动功能的改善和神经活动的增加表明，强迫运动可能正在改变PD患者的大脑功能。这个项目的目标是确定和比较强迫运动和自愿运动对帕金森病运动和非运动功能的影响，以及神经活动模式的相关变化。我们建议进行一项单中心、平行分组、病例对照、评分者盲法研究。该项目将是我们利用人类帕金森病患者的临床和客观生物力学结果直接比较强迫运动和自愿运动对运动和非运动功能的影响的努力的继续。总共100名轻中度特发性帕金森病患者将被随机分为自愿、强制或不锻炼对照组。临床和生物力学评估将在五个时间点进行：基线、治疗中期、治疗结束(EOT)、EOT+4和EOT+8周。据假设，与自愿和不锻炼组相比，完成强迫锻炼的患者将显示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，它可能成为药物或手术方法的一种可行的替代或辅助治疗方法。拟议的自行车干预措施简单，可以自我指导，相对便宜(消费版约2500美元)，可以立即转换到住院或门诊诊所或患者家中。

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.