Improving overground walking in people with chronic, incomplete spinal cord injury (iSCI) is especially important for older adults, who now represent more than 40% of the SCI population. Age and injury appear to interact to limit neuroplasticity in spared pathways, constraining gains from gait training. Brief episodes of low oxygen breathing (therapeutic acute intermittent hypoxia tAIH) may function as a plasticity-promoting primer to enhance the effects of transcutaneous spinal stimulation-augmented gait training (WALK tSTIM ), particularly in older individuals. This multicenter, age-stratified, placebo-controlled clinical trial will examine dose- and age-dependent effects of tAIH+WALK tSTIM on walking recovery in 60 adults with chronic (>1 year) iSCI. After an eight-session WALK prewash phase, participants are randomized within age strata (18-49 and 50-80 years) to tAIH+WALK tSTIM or Placebo+WALK tSTIM . The active intervention delivers daily tAIH or Placebo immediately before a 45-min WALK tSTIM session, 4 days per week for 4 weeks. Primary outcomes are walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up-and-Go), assessed at baseline, during intervention weeks, and 1, 4, and 8 weeks post intervention. Safety and mechanistic measures include lower extremity strength, spasticity, pain, cardiopulmonary function, cognition, autonomic events, and serum testosterone. Findings will determine whether tAIH priming augments WALK tSTIM relative to Placebo, whether extending pretreatment from 2 to 4 weeks (in pooled analyses with BO 2 ST-I) yields larger or more durable walking gains, and whether age and hormone levels modify responsiveness. These results will inform age-appropriate tAIH dosing strategies and support the development of personalized neuromodulatory rehabilitation for an aging SCI population.
Wall et al. (Thu,) studied this question.