Daily acute intermittent hypoxia to improve walking function in persons with subacute spinal cord injury: a randomized clinical trial study protocol

• Authors: Avantika Naidu, Harvard Medical School; Denise M. Peters, University of Vermont; Andrew Q. Tan, Harvard Medical School; Stella Barth, Spaulding Rehabilitation Hospital; Andrea Crane, Spaulding Rehabilitation Hospital; Angela Link, Spaulding Rehabilitation Hospital; Swapna Balakrishnan, Spaulding Rehabilitation Hospital; Heather B. Hayes, Emory University; Chloe Slocum, Harvard Medical School; Ross D. Zafonte, Harvard Medical School; Randy Trumbower, Emory University
• Journal Title: BMC Neurology
• Volume: Volume 20, Number 1
• Publisher: BMC Publishing | 2020-07-08, Pages 273-273
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1186/s12883-020-01851-9
• Subjects: Biology, Neuroscience; Health Sciences, Rehabilitation and Therapy; Biology, Physiology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Clinical Neurology; Neurosciences & Neurology; Intermittent hypoxia; Spinal cord injury; Spinal cord trauma; Plasticity; Low oxygen; Locomotion; Speed; Endurance; Walking; Hypertensive therapy; Enhances walking; Motor function; Plasticity; Recovery; SCI; Intervention; Pretreatment; Locomotion; Validity

Abstract

Background Restoring community walking remains a highly valued goal for persons recovering from traumatic incomplete spinal cord injury (SCI). Recently, studies report that brief episodes of low-oxygen breathing (acute intermittent hypoxia, AIH) may serve as an effective plasticity-inducing primer that enhances the effects of walking therapy in persons with chronic (> 1 year) SCI. More persistent walking recovery may occur following repetitive (weeks) AIH treatment involving persons with more acute SCI, but this possibility remains unknown. Here we present our clinical trial protocol, designed to examine the distinct influences of repetitive AIH, with and without walking practice, on walking recovery in persons with sub-acute SCI (< 12 months) SCI. Our overarching hypothesis is that daily exposure (10 sessions, 2 weeks) to AIH will enhance walking recovery in ambulatory and non-ambulatory persons with subacute (< 12 months) SCI, presumably by harnessing endogenous mechanisms of plasticity that occur soon after injury. Methods To test our hypothesis, we are conducting a randomized, placebo-controlled clinical trial on 85 study participants who we stratify into two groups according to walking ability; those unable to walk (non-ambulatory group) and those able to walk (ambulatory group). The non-ambulatory group receives either daily AIH (15, 90s episodes at 10.0% O2 with 60s intervals at 20.9% O2) or daily SHAM (15, 90s episodes at 20.9% O2 with 60s intervals at 20.9% O2) intervention. The ambulatory group receives either 60-min walking practice (WALK), daily AIH + WALK, or daily SHAM+WALK intervention. Our primary outcome measures assess overground walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up & Go Test). For safety, we also measure levels of pain, spasticity, systemic hypertension, and autonomic dysreflexia. We record outcome measures at baseline, days 5 and 10, and follow-ups at 1 week, 1 month, 6 months, and 12 months post-treatment. Discussion The goal of this clinical trial is to reveal the extent to which daily AIH, alone or in combination with task-specific walking practice, safely promotes persistent recovery of walking in persons with traumatic, subacute SCI. Outcomes from this study may provide new insight into ways to enhance walking recovery in persons with SCI.