To evaluate if acute intermittent hypoxia (AIH) coupled with transcutaneous spinal cord stimulation (tSCS) enhances task-specific training and leads to superior and more sustained gait improvements as compared with each of these strategies used in isolation in persons with chronic, incomplete spinal cord injury. Proof of concept, randomized crossover trial. Outpatient, rehabilitation hospital. Ten participants completed 3 intervention arms: (1) AIH, tSCS, and gait training (AIH plus tSCS); (2) tSCS plus gait training (SHAM AIH plus tSCS); and (3) gait training alone (SHAM plus SHAM). Each arm consisted of 5 consecutive days of intervention with a minimum of a 4-week washout between arms. The order of arms was randomized. The study took place from December 3, 2020, to January 4, 2023. 10-meter walk test at self-selected velocity (SSV) and fast velocity, 6-minute walk test, timed Up and Go (TUG) and secondary outcome measures included isometric ankle plantarflexion and dorsiflexion torque TUG improvements were 3.44 seconds (95% CI 1.24 to 5.65) significantly greater in the AIH plus tSCS arm than the SHAM AIH plus tSCS arm at post-intervention (POST), and 3.31 seconds (95% CI 1.03 to 5.58) greater than the SHAM plus SHAM arm at 1-week follow up (1WK). SSV was 0.08 m/s (95% CI 0.02 to 0.14) significantly greater following the AIH plus tSCS arm than the SHAM AIH plus tSCS at POST. Although not significant, the AIH plus tSCS arm also demonstrated the greatest average improvements compared with the other 2 arms at POST and 1WK for the 6-minute walk test, fast velocity, and ankle plantarflexion torque. This pilot study is the first to demonstrate that combining these 3 neuromodulation strategies leads to superior improvements in the TUG and SSV for individuals with chronic incomplete spinal cord injury and warrants further investigation.

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