ABSTRACT
Brief episodes of low oxygen breathing (therapeutic acute intermittent hypoxia; tAIH) may serve as an effective plasticity-promoting primer to enhance the effects of transcutaneous spinal stimulation-enhanced walking therapy (WALKtSTIM) in persons with chronic (>1 year) spinal cord injury (SCI). Pre-clinical studies in rodents with SCI show that tAIH and WALKtSTIM therapies harness complementary mechanisms of plasticity to maximize walking recovery. Here, we present a multi-site clinical trial protocol designed to examine the influence of tAIH + WALKtSTIM on walking recovery in persons with chronic SCI. We hypothesize that daily (eight sessions, 2 weeks) tAIH + WALKtSTIM will elicit faster, more persistent improvements in walking recovery than either treatment alone. To test our hypothesis, we are conducting a placebo-controlled clinical trial on 60 SCI participants who randomly receive one of three interventions: tAIH + WALKtSTIM; Placebo + WALKtSTIM; and tAIH + WALKtSHAM. Participants receive daily tAIH (fifteen 90-sec episodes at 10% O2 with 60-sec intervals at 21% O2) or daily placebo (fifteen 90-sec episodes at 21% O2 with 60-sec intervals at 21% O2) before a 45-min session of WALKtSTIM or WALKtSHAM. Our primary outcome measures assess walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up and Go Test). For safety, we also measure pain levels, spasticity, sleep behavior, cognition, and rates of systemic hypertension and autonomic dysreflexia. Assessments occur before, during, and after sessions, as well as at 1, 4, and 8 weeks post-intervention. Results from this study extend our understanding of the functional benefits of tAIH priming by investigating its capacity to boost the neuromodulatory effects of transcutaneous spinal stimulation on restoring walking after SCI. Given that there is no known cure for SCI and no single treatment is sufficient to overcome walking deficits, there is a critical need for combinatorial treatments that accelerate and anchor walking gains in persons with lifelong SCI. Trial Registration: ClinicalTrials.gov, NCT05563103.
ABSTRACT
Humans routinely modify their walking speed to adapt to functional goals and physical demands. However, damage to the central nervous system (CNS) often results in abnormal modulation of walking speed and increased risk of falls. There is considerable interest in treatment modalities that can provide safe and salient training opportunities, feedback about walking performance, and that may augment less reliable sensory feedback within the CNS after injury or disease. Fully immersive virtual reality technologies show benefits in boosting training-related gains in walking performance; however, they lack views of the real world that may limit functional carryover. Augmented reality and mixed reality head-mount displays (MR-HMD) provide partially immersive environments to extend the virtual reality benefits of interacting with virtual objects but within an unobstructed view of the real world. Despite this potential advantage, the feasibility of using MR-HMD visual feedback to promote goal-directed changes in overground walking speed remains unclear. Thus, we developed and evaluated a novel mixed reality application using the Microsoft HoloLens MR-HMD that provided real-time walking speed targets and augmented visual feedback during overground walking. We tested the application in a group of adults not living with disability and examined if they could use the targets and visual feedback to walk at 85%, 100%, and 115% of each individual's self-selected speed. We examined whether individuals were able to meet each target gait speed and explored differences in accuracy across repeated trials and at the different speeds. Additionally, given the importance of task-specificity to therapeutic interventions, we examined if walking speed adjustment strategies were consistent with those observed during usual overground walking, and if walking with the MR-HMD resulted in increased variability in gait parameters. Overall, participants matched their overground walking speed to the target speed of the MR-HMD visual feedback conditions (all p-values > 0.05). The percent inaccuracy was approximately 5% across all speed matching conditions and remained consistent across walking trials after the first overall walking trial. Walking with the MR-HMD did not result in more variability in walking speed, however, we observed more variability in stride length and time when walking with feedback from the MR-HMD compared to walking without feedback. The findings offer support for mixed reality-based visual feedback as a method to provoke goal-specific changes in overground walking behavior. Further studies are necessary to determine the clinical safety and efficacy of this MR-HMD technology to provide extrinsic sensory feedback in combination with traditional treatments in rehabilitation.
