The Cyclical Lower-extremity Exercise for Parkinson's Trial

帕金森氏症试验的周期性下肢运动

• 批准号: 8733774
• 负责人: JAY L. ALBERTS
• 金额: $ 35.41万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8733774
• 关键词: Acute; Adverse effects; Aerobic; Animal Experiments; Animals; Back; Biomechanics; Blinded; Brain; Clinical; Control Groups; Data; Development; Dopamine; Effectiveness; Exercise; Exhibits; Functional Magnetic Resonance Imaging; Goals; Home environment; Human; Inpatients; Intervention; Levodopa; Lower Extremity; Measures; Mechanics; Medical; Meta-Analysis; Modeling; Motor; Movement; Movement Disorders; Operative Surgical Procedures; Outcome; Outcome Measure; Outpatients; Parkinson Disease; Patients; Pattern; Physical therapy exercises; Quality of life; Randomized; Recommendation; Rodent; Short-Term Memory; Societies; Stimulus; Testing; Therapeutic; Time; Trail Making Test; Translating; base; blind; case control; dopaminergic neuron; executive function; follow-up; improved; motor function improvement; neural patterning; neurotrophic factor; non-drug; non-motor symptom; primary outcome; relating to nervous system; research study; secondary outcome

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.

描述（由申请人提供）：当前的医疗和手术方法很昂贵，并且与可能损害患者生活质量的各种副作用有关。提高非毒品，非手术治疗方法来改善运动功能的方法将为当前的PD治疗方法提供有吸引力的辅助手段。动物研究表明，强迫运动可以提高运动功能并具有神经保护性。我们假设人与动物实验之间明显的矛盾结果是所使用的运动范式差异的结果。人类的实验是自愿的，而强制运动则用于动物。 PD模型为PD患者使用强制运动干预提供了理论框架和理由。运动激活的降低可能会限制PD患者以基于动物研究的必要速度产生自愿运动的能力，以改善全球运动功能。我们开发了安全的下肢强制运动范式，以增加PD患者的自愿运动，以帮助他们安全地实现大于自愿率的运动率。我们R21项目的结果表明，完成为期8周的强迫运动干预措施的患者的临床运动评分评分占25％，而完成的自愿运动干预（类似的有氧强度）的患者在临床等级方面却没有改善。我们最近的功能磁共振成像数据表明，PD患者的强制运动产生类似的皮质下和皮质激活模式，如左旋多巴后所见。运动功能的全球改善和神经活动的增加表明，强制运动可能正在改变PD患者的大脑功能。该项目的目的是确定和比较强制与自愿运动对PD电机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，平行组，病例对照，评估的研究。该项目将继续我们的努力直接比较强制和自愿运动对人类PD患者中临床和客观生物力学结果对运动和非运动功能的影响。共有100名轻度至中度特发性PD患者将被随机分为自愿，强迫或无运动对照组。临床和生物力学评估将在五个时间点进行：基线，中期治疗，治疗结束（EOT），EOT + 4和EOT + 8周。假设完成强迫运动的患者与自愿和无运动组相比，运动功能的全球性运动功能和非运动症状减少。如果强制运动有效，则可能成为药理学或手术方法的可行替代或辅助疗法。拟议的骑自行车干预很简单，可以自我指导，相对便宜（消费者版本约为2500美元），并且可以立即转化为住院或门诊临床环境或患者的家。