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: 10650394
• 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/10650394
• 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; 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; Persons; Pharmaceutical Preparations; Pharmacotherapy; Randomized; 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; axon injury; axonal degeneration; clinical outcome measures; design; dexterity; disability; disability impact; exercise adherence; exercise intervention; experience; falls; foot; improved; improved mobility; multimodality; multiple sclerosis patient; muscle strength; myelination; nervous system disorder; neurological rehabilitation; neuroprotection; novel imaging technique; pharmacologic; prevent; primary outcome; randomized, clinical trials; 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.

项目摘要/摘要 多发性硬化症（MS）是一种常见的神经系统疾病，可能导致活性和 参与。 MS是由间歇性炎症引起的，导致脱髓鞘和轴突损伤。这 促进再髓样是一种有希望的治疗策略，可以克服和防止MS残疾 改善动作电位的传导速度并为轴突提供神经保护绝缘。 有效的再髓系可能需要采用多模式的方法，包括康复和药理学 疗法，以刺激沿着神经途径的再髓式。在MS动物模型中，有氧运动可以 单独促进或通过药物疗法协同促进透明度。但是，目前尚不确定如何 衡量MS患者的雷旋，并且缺乏可再现和可靠的髓磷脂状态 是开发再髓疗法的主要障碍。在成功发展之前 大规模的多模式临床试验，至关重要的需要1）确定评估最佳结果 再髓样的范围，2）证明了康复性有氧运动的可行性和研究设计 干涉。 这项研究的中心假设是1）MS中的脊髓脱髓鞘，如延长测量 体感的诱发电位（SSEP）潜伏期与功能，活动和活动的降低相关 参与MS和2）有氧固定骑自行车是安全且可行的康复 干预MS的人以改善移动性。除了解决这些假设之外，我们还将聚集 有氧运动对SSEP潜伏期，步行速度和其他措施的初步数据 活动和参与。 SSEP是一个理想的客观措施，因为它们便宜，可重复， 市售，并提供反映脊髓中髓鞘化的功能措施。这 拟议的研究将探索SSEP评估的髓鞘形成之间的关联和 身体结构，功能，活动和参与的结果度量，以确定最佳的临床结果 监测透明度。这项研究还将确定24周有氧运动的安全性和可行性 与MS症状教育控制干预措施相比 MS患者的单盲，平行临床试验。实验目标将探索有氧静止 骑自行车与脊髓的迁移率和恢复性的改善有关，如 SSEP。这项研究的目的是奠定设计和实施未来R01资助的未来所需的基础工作 有氧固定循环和药物治疗的多模式，随机临床试验刺激 MS患者的再髓。

项目成果

Diffusion basis spectrum imaging and diffusion tensor imaging predict persistent black hole formation in multiple sclerosis.

扩散基谱成像和扩散张量成像预测多发性硬化症中持续黑洞的形成。

• DOI: 10.1016/j.msard.2024.105494
• 发表时间: 2024
• 期刊: Multiple sclerosis and related disorders
• 影响因子: 4
• 作者: Wooliscroft,Lindsey;Salter,Amber;Adusumilli,Gautam;Levasseur,VictoriaA;Sun,Peng;Lancia,Samantha;Perantie,DanaC;Trinkaus,Kathryn;Naismith,RobertT;Song,Sheng-Kwei;Cross,AnneH
• 通讯作者: Cross,AnneH