Low-Load Resistance Training with Blood Flow Restriction in People with Multiple Sclerosis and Advanced Disability: A Randomized Control Trial

多发性硬化症和严重残疾患者的低负荷阻力训练和血流限制：随机对照试验

• 批准号: 10536164
• 负责人: Mark M Manago
• 金额: --
• 依托单位: VA EASTERN COLORADO HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-11-01 至 2027-10-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10536164
• 关键词: Address; Affect; American; Anaerobic Bacteria; Ankle; Area; Award; Biological Markers; Blinded; Blood flow; Cell Proliferation; Chronic; Clinical; Clinical Trials; Colorado; Control Groups; Data; Devices; Disease Progression; Elderly; Exercise; Fatigue; Future; Goals; Health; Healthcare Systems; Hip region structure; Human Resources; Hypertrophy; Hypoxia; Infrastructure; Intervention; Knee; Laboratories; Leadership; Limb structure; Measures; Mechanical Stress; Mechanics; Mentorship; Metabolism; Morphology; Multiple Sclerosis; Muscle; Muscle Fatigue; Muscle Weakness; Musculoskeletal; Outcome; Outcome Assessment; Participant; Patient Self-Report; Performance; Persons; Phase; Phase II Clinical Trials; Population; Protein Biosynthesis; Quality of life; Randomized; Randomized Controlled Trials; Research; Research Personnel; Research Project Grants; Resistance; Resources; Role; Science; Single-Blind Study; Symptoms; Thick; Time; Training; Training Programs; Veterans; Walking; Wheelchairs; Woman; clinical center; clinical translation; comparative effectiveness study; disability; education research; efficacy evaluation; efficacy study; efficacy trial; exercise intensity; exercise intervention; experimental group; follow-up; functional group; improved; improved mobility; innovation; men; multiple sclerosis patient; muscle form; muscle hypertrophy; muscle strength; nervous system disorder; novel; physical conditioning; post intervention; pressure; prevent; primary endpoint; primary outcome; quadriceps muscle; rehabilitative care; response; safety and feasibility; satellite cell; screening; skills; strength training

Multiple Sclerosis (MS) is a chronic neurological disorder affecting about 1 million Americans. MS is typically more aggressive in men than women, thus Veterans, being mostly men, often have more severe symptoms, worse mobility, and more advanced disability compared to non-Veterans with MS. Among the many MS symptoms, muscle weakness is among the most common, contributes to decreased mobility, and worsens as disability advances. While there is strong evidence that moderate-to-high intensity resistance training improves muscle strength in people with MS and low disability, there is little evidence evaluating resistance training in people with advanced disability due to MS (i.e., those who need assistance to walk or use a wheelchair). People with advanced disability due to MS require unique approaches to resistance training as they often cannot tolerate higher intensity exercise because of severe weakness and fatigue. Blood flow restriction (BFR) has the potential to address these issues. With BFR, resistance training at low intensities has been shown to be as effective as high intensity training without BFR at increasing muscle strength and hypertrophy in people with a variety of musculoskeletal conditions. Our team also has preliminary data to support the safety, feasibility, and tolerance of BFR resistance training in people with advanced disability due to MS. The objective of the currently proposed study is to evaluate the efficacy of low-load resistance training with BFR on muscle strength, mobility, and fatigue in people with advanced disability due to MS. This proposed Phase II clinical trial would be the first to study the efficacy of low-load resistance training with BFR in people with MS and would address a crucial gap that is highly relevant for Veterans with MS: interventions to improve mobility and optimize function for those with advanced disability. Fifty-eight participants with MS and advanced disability will be randomized (1:1) to low-load resistance training with BFR (experimental) or without BFR (control). Resistance training will target knee and hip extension, knee and hip flexion, and ankle plantarflexion 2x/week for 10 weeks. A blinded assessor will collect outcomes at baseline, post-intervention (primary endpoint), and after 8 weeks of follow-up. The Study Aims are to determine between-group differences in 1) Muscle health: quadriceps strength (primary outcome) and muscle morphology (thickness and echogenicity); 2) Mobility: 30-Second Sit-to-Stand; and 3) Self-reported fatigue: Modified Fatigue Impact Scale. We hypothesize that the experimental group will have significantly greater improvements in muscle strength and thickness, mobility, and self-reported fatigue compared to the control group. The long-term goal of this research is to develop clinically feasible exercise interventions for people with advanced disability due to MS that can improve participation, quality of life, and disability. In addition to leading the research project, the candidate will leverage protected time to develop research, technical, and leadership skills essential for a future role as a VA independent investigator with expertise in developing, optimizing, and implementing interventions that improve participation, quality of life, and physical health outcomes in people with MS and other populations with disability. During the training portion of this award the candidate will develop expertise in 1) sonographic assessment of muscle morphology, 2) the use of biomarker analysis to measure the impact of exercise in people with MS, and 3) science leadership. The training and research will be supported by the personnel, resources, and infrastructure at the Geriatric Research Education and Clinical Center of the VA Eastern Colorado Health Care System. Specifically, the screening, outcome assessments, and intervention will take place in the Muscle Morphology, Mechanics, and Performance Laboratory. Additional mentorship and support will be provided remotely from the VA Portland Health Care System and the VA MS Centers of Excellence-West.

多发性硬化症 (MS) 是一种慢性神经系统疾病，影响约 100 万美国人。多发性硬化症通常是 男性比女性更具攻击性，因此退伍军人大多是男性，往往有更严重的症状， 与患有多发性硬化症的非退伍军人相比，行动能力更差，残疾更严重。在众多MS中 症状中，肌肉无力是最常见的症状之一，会导致活动能力下降，并且会随着时间的推移而恶化 残疾进步。虽然有强有力的证据表明中等到高强度的阻力训练可以改善 对于多发性硬化症和低残疾患者的肌肉力量，几乎没有证据评估阻力训练 因多发性硬化症而患有严重残疾的人（即需要帮助行走或使用轮椅的人）。 因多发性硬化症而患有严重残疾的人需要独特的阻力训练方法，因为他们经常 由于严重虚弱和疲劳，无法忍受较高强度的运动。血流限制（BFR） 有潜力解决这些问题。通过 BFR，低强度的阻力训练已被证明可以 在增加人体肌肉力量和肥大方面与无 BFR 的高强度训练一样有效 具有各种肌肉骨骼状况。我们的团队也有初步数据来支持安全性， 对于因多发性硬化症而患有严重残疾的人来说，BFR 阻力训练的可行性和耐受性。目标 目前提出的研究的目的是评估 BFR 低负荷阻力训练对肌肉的功效 因多发性硬化症而患有严重残疾的人的力量、活动能力和疲劳。 这项拟议的 II 期临床试验将是第一个研究低负荷阻力训练效果的试验 多发性硬化症患者的 BFR 可以解决与多发性硬化症退伍军人高度相关的一个关键差距： 旨在改善重度残疾者的活动能力和优化功能的干预措施。五十八 患有多发性硬化症和严重残疾的参与者将被随机 (1:1) 接受 BFR 低负荷阻力训练 （实验）或无 BFR（对照）。阻力训练的目标是膝关节和髋关节的伸展、膝关节和髋关节 屈曲和踝关节跖屈 2 次/周，持续 10 周。盲法评估员将收集基线结果， 干预后（主要终点）和 8 周随访后。研究目的是确定 1) 肌肉健康方面的组间差异：股四头肌力量（主要结果）和肌肉 形态（厚度和回声）； 2) 活动能力：30 秒从坐到站； 3) 自我报告的疲劳： 修改后的疲劳影响量表。我们假设实验组将有显着更大的 与对照组相比，肌肉力量和厚度、活动能力和自我报告的疲劳程度有所改善 团体。这项研究的长期目标是为患有以下疾病的人开发临床上可行的运动干预措施 多发性硬化症导致的严重残疾可以改善参与度、生活质量和残疾。 除了领导研究项目外，候选人还将利用受保护的时间来开展研究， 技术和领导技能对于未来担任 VA 独立调查员至关重要，具有以下专业知识 制定、优化和实施改善参与、生活质量和身体素质的干预措施 多发性硬化症患者和其他残疾人群的健康结果。在本次培训部分 授予候选人将发展以下方面的专业知识：1）肌肉形态的超声评估，2）使用 生物标志物分析来衡量运动对多发性硬化症患者的影响，3) 科学领导力。这 培训和研究将得到老年医学中心的人员、资源和基础设施的支持 VA 东科罗拉多州医疗保健系统研究教育和临床中心。具体来说， 筛选、结果评估和干预将在肌肉形态学、力学和 性能实验室。弗吉尼亚州波特兰分校将远程提供额外的指导和支持 医疗保健系统和 VA MS 卓越中心 - 西部。