Aerobic exercise to improve mobility in multiple sclerosis: optimizing design and execution for a full-scale multimodal remyelination clinical trial

有氧运动改善多发性硬化症的活动能力：优化全面多模式髓鞘再生临床试验的设计和执行

• 批准号: 10164840
• 负责人: Lindsey Brianna Wooliscroft
• 金额: $ 15.97万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10164840
• 关键词: Action Potentials; Address; Aerobic; Aerobic Exercise; Affect; Animal Model; Axon; Biological Markers; Body measure procedure; Clinical; Clinical Trials; Clinical Trials Cooperative Group; Collaborations; Complement; Control Groups; Data; Demyelinations; Development; Education; Electrophysiology (science); Enrollment; Ensure; Exercise; Failure; Feasibility Studies; Frequencies; Funding; Future; Goals; Impairment; Inflammation; Intervention; Lower Extremity; Measures; Monitor; Multicenter Trials; Multiple Sclerosis; Myelin; Nerve Fibers; Neural Pathways; Neurologic; Neurons; Outcome; Outcome Measure; Patient Outcomes Assessments; Patient Self-Report; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Randomized; Randomized Clinical Trials; Recurrence; Rehabilitation therapy; Reproducibility; Research; Research Design; Sample Size; Single-Blind Study; Somatosensory Evoked Potentials; Spinal Cord; Spinal Remyelination; Structure; Supervision; Symptoms; Testing; Therapeutic; Time; Upper Extremity; Walking; Work; active control; axon injury; axonal degeneration; clinical outcome measures; design; dexterity; disability; disability impact; exercise adherence; exercise intervention; experience; falls; foot; improved; improved mobility; multimodality; muscle strength; myelination; nervous system disorder; neurological rehabilitation; novel imaging technique; prevent; primary outcome; rehabilitation strategy; remyelination; repaired; safety and feasibility; walking speed; young adult

PROJECT SUMMARY/ABSTRACT Multiple sclerosis (MS) is a common neurologic disease that can result in significant restriction in activity and participation. MS is caused by intermittent inflammation causing demyelination and axonal damage. The promotion of remyelination is a promising therapeutic strategy to overcome and prevent MS disability by improving the conduction velocity of action potentials and providing neuroprotective insulation for the axon. Effective remyelination will likely require a multimodal approach, including rehabilitative and pharmacologic therapies, to stimulate remyelination along neural pathways. In animal models of MS, aerobic exercise can promote remyelination alone or synergistically with pharmacotherapy. However, it is currently uncertain how to measure remyelination in people with MS and this lack of a reproducible and reliable measure of myelin status is a major obstacle to the development of remyelination therapies. Prior to the successful development of large-scale multimodal clinical trials, there is a crucial need to 1) determine the optimal outcomes to assess the extent of remyelination, and 2) demonstrate the feasibility and study design of a rehabilitative aerobic exercise intervention. The central hypotheses of this study are that 1) spinal cord demyelination in MS, as measured by prolongation of somatosensory evoked potential (SSEP) latency, is associated with reduced function, activity and participation in people with MS, and 2) aerobic stationary cycling is a safe and feasible rehabilitative intervention in people with MS to improve mobility. Besides addressing these hypotheses, we will gather preliminary data on the effects of aerobic exercise on SSEP latencies, walking speed, and other measures of activity and participation. SSEPs are an ideal objective measure as they are inexpensive, reproducible, commercially available, and provide a functional measure reflecting myelination in the spinal cord. This proposed study will explore the association between myelination, as assessed by SSEPs, and a panel of outcome measures of body structure, function, activity and participation, to determine optimal clinical outcomes to monitor remyelination. This study will also determine the safety and feasibility of a 24-week aerobic stationary cycling intervention as compared to an MS symptom education control intervention in a randomized, single-blind, parallel clinical trial in people with MS. An experimental aim will explore if aerobic stationary cycling is associated with improvements in mobility and remyelination of the spinal cord, as measured by SSEP. The goal of this study is to lay the ground work needed to design and implement a future, R01-funded, multimodal, randomized clinical trial of aerobic stationary cycling and pharmacotherapy to stimulate remyelination in people with MS.

项目总结/摘要 多发性硬化症（MS）是一种常见的神经系统疾病，可导致活动明显受限， 参与的多发性硬化症是由间歇性炎症引起脱髓鞘和轴突损伤。的 促进髓鞘再生是一种很有前途的治疗策略，可以通过以下方式克服和预防MS残疾： 提高动作电位的传导速度，为轴突提供神经保护性绝缘。 有效的髓鞘再生可能需要多种方法，包括康复和药物治疗。 治疗，以刺激髓鞘再生沿着神经通路。在多发性硬化症的动物模型中，有氧运动可以 单独或与药物疗法协同促进髓鞘再生。然而，目前还不确定如何 测量MS患者的髓鞘再生，缺乏可重复和可靠的髓鞘状态测量 是髓鞘再生疗法发展的主要障碍。在成功开发 在大规模多模式临床试验中，迫切需要1）确定最佳结果以评估 髓鞘再生的程度; 2）证明康复有氧运动的可行性和研究设计 干预 本研究的中心假设是：1）MS中的脊髓脱髓鞘，通过延长 体感诱发电位（SSEP）潜伏期的延长与功能、活动和 参与MS患者，和2）有氧固定自行车是一种安全可行的康复方法 对MS患者进行干预，以改善活动能力。除了解决这些假设，我们将收集 有氧运动对SSEP潜伏期、步行速度和其他指标影响的初步数据， 活动和参与。SSEP是一种理想的客观测量方法，因为它们价格低廉，可重复， 可商购获得，并提供反映脊髓中髓鞘形成的功能测量。这 拟议的研究将探讨髓鞘形成之间的关联，如SSEP评估，和一组 身体结构、功能、活动和参与的结局指标，以确定最佳临床结局 监测髓鞘再生这项研究还将确定24周有氧运动的安全性和可行性。 在一个随机， 在MS患者中进行的单盲、平行临床试验。实验目的是探索有氧静止 骑自行车与脊髓活动性和髓鞘再生的改善有关， SSEP。本研究的目标是为设计和实施未来的R 01资助的， 有氧静止自行车和药物治疗刺激的多模式随机临床试验 多发性硬化症患者的髓鞘再生