A multimodality intervention to improve musculoskeletal health, function, metabolism, and well-being in spinal cord injury: study protocol for the FIT-SCI randomized controlled trial

K F Reid, T W Storer, K M Pencina, R Valderrabano, N K Latham, L Wilson, C Ghattas, R Dixon, A Nunes, N Bajdek, G Huang, S E Skeels, A P Lin, S M Merugumala, H J Liao, M L Bouxsein, R D Zafonte, S Bhasin, K F Reid, T W Storer, K M Pencina, R Valderrabano, N K Latham, L Wilson, C Ghattas, R Dixon, A Nunes, N Bajdek, G Huang, S E Skeels, A P Lin, S M Merugumala, H J Liao, M L Bouxsein, R D Zafonte, S Bhasin

Abstract

Background: A spinal cord injury (SCI) is a devastating, life-changing event that has profoundly deleterious effects on an individual's health and well-being. Dysregulation of neuromuscular, cardiometabolic, and endocrine organ systems following an SCI contribute to excess morbidity, mortality and a poor quality of life. As no effective treatments currently exist for SCI, the development of novel strategies to improve the functional and health status of individuals living with SCI are much needed. To address this knowledge gap, the current study will determine whether a Home-Based Multimodality Functional Recovery and Metabolic Health Enhancement Program that consists of functional electrical stimulation of the lower extremity during leg cycling (FES-LC) plus arm ergometry (AE) administered using behavioral motivational strategies, and testosterone therapy, is more efficacious than FES-LC plus AE and placebo in improving aerobic capacity, musculoskeletal health, function, metabolism, and wellbeing in SCI.

Methods: This single-site, randomized, placebo-controlled, parallel group trial will enroll 88 community-dwelling men and women, 19 to 70 years of age, with cervical and thoracic level of SCI, ASIA Impairment Scale grade: A, B, C, or D, 6 months or later after an SCI. Participants randomized to the multimodality intervention will undergo 16 weeks of home-based FES-LC and AE training plus testosterone undecanoate. Testosterone undecanoate injections will be administered by study staff in clinic or by a visiting nurse in the participant's home. The control group will receive 16 weeks of home-based FES-LC and AE exercise plus placebo injections. The primary outcome of this trial is peak aerobic capacity, measured during an incremental exercise testing protocol. Secondary outcomes include whole body and regional lean and adipose tissue mass; muscle strength and power; insulin sensitivity, lipids, and inflammatory markers; SCI functional index and wellbeing (mood, anxiety, pain, life satisfaction and depressive symptoms); and safety.

Discussion: We anticipate that a multimodality intervention that simultaneously addresses multiple physiological impairments in SCI will result in increased aerobic capacity and greater improvements in other musculoskeletal, metabolic, functional and patient-reported outcomes compared to the control intervention. The findings of this study will have important implications for improving the care of people living with an SCI.

Trial registration: ClinicalTrials.gov : ( NCT03576001 ). Prospectively registered: July 3, 2018.

Keywords: Androgen therapy; Exercise; Multimodality intervention; Spinal cord injury.

Conflict of interest statement

SB reports receiving research grant support from AbbVie, Transition Therapeutics, FPT, and Metro International Biotechnology, Inc. and has received consulting fees from OPKO Pharmaceuticals and POXEL, Inc., and has equity interest in FPT, LLC and Xyone Therapeutics. Other authors report no conflicts of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flowchart of trial participation
Fig. 2
Fig. 2
Conceptual Model for Hypothesized Effects of Multimodality Intervention in SCI. Exercise (FES-LC + AE) and testosterone may individually increase aerobic capacity, and muscle mass and strength, which would improve physical function and wellbeing. Exercise or testosterone may also enhance metabolic adaptations directly through effects on muscle mass and contractility mediated via myokines, fuel utilization, and other mechanisms, and indirectly via increased activity. Testosterone may directly affect metabolism and wellbeing. When combined, the synergistic effects of the multimodality intervention (FES-LC + AE + testosterone) may induce greater benefits compared to each intervention alone (as shown by larger solid arrows)

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