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，影响着大约100万美国人。MS通常是 男性比女性更具攻击性，因此退伍军人，主要是男性，通常有更严重的症状， 与患有多发性硬化症的非退伍军人相比，MS患者的机动性更差，残疾程度更高。 症状，肌肉无力是最常见的症状之一，导致活动能力下降，并随着 伤残预付款。虽然有强有力的证据表明，中到高强度的耐力训练可以改善 MS和低残疾人群的肌肉力量，几乎没有证据评估阻力训练 患有多发性硬化症的严重残疾人士(即需要协助行走或使用轮椅的人士)。 患有多发性硬化症的严重残疾患者需要独特的阻力训练方法，因为他们经常 不能忍受高强度的运动，因为严重的虚弱和疲劳。血流限制(BFR) 有可能解决这些问题。对于BFR，低强度的阻力训练已经被证明是 在增加人的肌肉力量和肥大方面，与没有BFR的大强度训练一样有效 有各种肌肉骨骼状况。我们团队也有支持安全性的初步数据， 对多发性硬化症晚期残疾患者进行BFR抵抗训练的可行性和耐受性。 目前提出的一项研究是评估低负荷阻力训练对肌肉的效果 多发性硬化症导致的严重残疾患者的力量、活动能力和疲劳。 这项拟议的第二阶段临床试验将是第一次研究低负荷耐力训练的有效性 BFR在多发性硬化症患者中的应用，并将解决与多发性硬化症退伍军人高度相关的一个关键差距： 为晚期残疾人改善行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)使用BFR进行低负荷阻力训练 (试验性)或不加BFR(对照组)。阻力训练的目标是膝盖和髋关节伸展，膝盖和髋关节 屈膝，踝关节屈膝，每周2次，共10周。盲人评估员将收集基线的结果， 干预后(主要终点)，8周后随访。这项研究的目的是确定 在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)活动度：30秒坐立；3)自我报告疲劳： 修改后的疲劳冲击标尺。我们假设试验组将有明显更多的 与对照组相比，肌肉力量和厚度、活动度和自我报告的疲劳程度都有所改善 一群人。这项研究的长期目标是为患有疾病的人开发临床可行的运动干预措施。 多发性硬化症引起的严重残疾，可以提高参与度、生活质量和残疾程度。 除了领导研究项目，候选人还将利用受保护的时间来开展研究， 作为一名具有以下专业知识的退伍军人管理局独立调查员，在未来担任调查员所必需的技术和领导技能 制定、优化和实施干预措施，以提高参与度、生活质量和身体素质 多发性硬化症患者和其他残疾人群的健康结果。在本课程的培训部分 获奖候选人将在1)超声评估肌肉形态方面发展专业知识，2)使用 生物标记物分析，以衡量运动对多发性硬化症患者的影响，以及3)科学领导力。这个 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 退伍军人事务部东科罗拉多州医疗保健系统研究、教育和临床中心。具体地说， 筛查、结果评估和干预将在肌肉形态、力学和 性能实验室。将从退伍军人管理局波特兰远程提供额外的指导和支持 医疗保健系统和退伍军人管理局卓越中心-WEST。