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。MS通常 男性比女性更具侵略性，因此退伍军人，大多数是男性，往往有更严重的症状， 更差的流动性，更先进的残疾相比，非退伍军人与MS。在许多MS 症状，肌肉无力是最常见的，有助于减少流动性，并作为 残疾进步。虽然有强有力的证据表明，中到高强度的阻力训练， 肌肉力量的人与MS和低残疾，有很少的证据评估阻力训练， 由于MS而具有晚期残疾的人（即，需要协助行走或使用轮椅的人士）。 患有MS的晚期残疾的人需要独特的阻力训练方法，因为他们通常 由于严重的虚弱和疲劳，不能忍受更高强度的运动。血流受限（BFR） 有可能解决这些问题。使用BFR，低强度的阻力训练已被证明 在增加人的肌肉力量和肥大方面，与没有BFR的高强度训练一样有效 患有各种肌肉骨骼疾病我们的团队也有初步的数据来支持安全性， BFR阻力训练的可行性和耐受性的人与先进的残疾，由于MS的目的 目前提出的研究的目的是评估低负荷抗阻训练与BFR对肌肉的效果 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的疗效， BFR在MS患者中的应用，将解决与MS退伍军人高度相关的关键差距： 干预措施，以改善流动性和优化功能，为那些有严重残疾。五十八 患有MS和晚期残疾的受试者将随机（1：1）接受BFR低负荷阻力训练 （实验）或无BFR（对照）。阻力训练将针对膝盖和髋关节伸展，膝盖和髋关节 屈曲和踝跖屈2次/周，持续10周。设盲评估者将收集基线时的结局， 干预后（主要终点）和8周随访后。研究目的是确定 组间差异：1）肌肉健康：股四头肌力量（主要结局）和肌肉 形态学（厚度和回声反射性）; 2）活动性：30秒坐立;和3）自我报告疲劳： 改良疲劳冲击量表。我们假设，实验组将有显着更大的 与对照组相比，肌肉强度和厚度、活动性和自我报告的疲劳有所改善 组这项研究的长期目标是为患有糖尿病的人开发临床可行的运动干预措施。 MS导致的晚期残疾，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， 制定、优化和实施干预措施，改善参与、生活质量和身体健康。 MS患者和其他残疾人群的健康结果。在培训期间， 授予候选人将发展的专业知识，1）超声评估肌肉形态，2）使用 生物标志物分析，以衡量运动对MS患者的影响，以及3）科学领导力。的 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。 弗吉尼亚州东部科罗拉多卫生保健系统的研究、教育和临床中心。具体而言是 筛选、结果评估和干预将在肌肉形态学、力学和 性能实验室。将从退伍军人事务部波特兰远程提供额外的指导和支持 卫生保健系统和弗吉尼亚州西部卫生保健中心。