Over 250,000 Americans are living with paralysis resulting from spinal cord injury (SCI), one of the most grievous events in a person's life. Inter-linked deficits in multiple physiologic organ systems in persons with SCI contribute to a vicious cycle of progressively declining musculoskeletal and cardiometabolic health, and wellbeing. In recognition of the profoundly deleterious effects of chronic SCI on an individual's health, the National Center for Medical Rehabilitation Research (NCMRR) has deemed ?pharmaceutical, stimulation, and exercise?strategies to improve the motor function and health of SCI patients? a priority area of research. The NCMRR has further emphasized efficacy trials of multicomponent interventions, as this application proposes to accomplish. There is evidence - mostly from nonrandomized studies - that arm ergometry and functional electrical stimulation of the lower extremity during leg cycling (FES-LC) improve physical capacity of SCI patients. However, the aerobic demands and workloads achieved by arm ergometry or FES-LC alone are often not of sufficient intensity to induce optimal musculoskeletal and metabolic adaptations. SCI is associated with high prevalence of androgen deficiency, which further contributes to muscle loss, metabolic dysregulation, and low mood. By combining FES-LC with concurrent arm ergometry (?hybrid? training), substantially higher levels of exercise intensity can be achieved than with either intervention alone. The effects of hybrid exercise on muscle mass, strength, and function are augmented by androgen administration. Furthermore, androgen may have additional beneficial effects in improving mood, wellbeing, pain sensitivity, and metabolic outcomes. We hypothesize that a Home-Based Multimodality Functional Recovery and Metabolic Health Enhancement Program that includes concurrent FES-LC and arm ergometry, and an androgen (19-nortestosterone decanoate, 19ND) would be more efficacious than arm ergometry alone in improving aerobic capacity, muscle mass and strength, metabolic health, self-reported function and mobility, and wellbeing. This hypothesis will be tested in a randomized trial in 84 persons with C7 to T12 SCI, AIS grade A, B or C, 6 months or later after SCI. Participants will be randomized to either the multi-modality intervention or arm ergometry alone for 16 weeks. After 2-weeks of training in the exercise laboratory, the intervention will be conducted in the participant's home, using video monitoring of the home exercise. Primary outcome is peak aerobic capacity. Secondary outcomes include self-reported function and mobility assessed using computerized adaptive test version of Spinal Cord Injury-Functional Index; muscle mass, strength and fatigability; fat mass and distribution; metabolism (insulin sensitivity; lipids; inflammatory markers); wellbeing (mood, anxiety, pain, and life satisfaction). An inter- disciplinary team, access to a large patient pool, rigorous trial design, assiduous attention to patient safety and statistical power, and inclusion of performance-based and patient-reported outcomes should facilitate the accomplishment of the proposed aims, which have implications for improving the care of SCI patients.
The National Center for Medical Rehabilitation Research (NCMRR) has deemed ?pharmaceutical, stimulation, and exercise?strategies to improve the motor function and health of SCI patients? a priority area of research, and has further emphasized efficacy trials of multicomponent interventions. In alignment with the priorities of the NCMRR and the public health need, the proposed randomized trial will determine the efficacy of a Home- Based Multimodality Functional Recovery and Metabolic Health Enhancement Program that includes functional electrical stimulation of the lower extremity during leg cycling, arm ergometry, and an androgen in comparison to a home-based arm ergometry alone and placebo in improving aerobic capacity, muscle mass and strength, metabolic health, self-reported function and mobility, and wellbeing in persons with SCI at C7 to T12 level, AIS grade A, B or C, 6 months or later after injury. The unique strengths of the application include a home-based multicomponent intervention, scientifically rigorous clinical trial design, an inter-disciplinary team, access to a large patient pool, assiduous attention to quality control, patient safety and statistical power, and inclusion of performance-based as well as patient-reported efficacy outcomes.
