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

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.