Acute Intermittent Hypoxia With High-Intensity Gait Training in Chronic Stroke: A Phase II Randomized Crossover Trial.

BACKGROUND: Studies in individuals with chronic stroke indicate high-intensity training (HIT) focused on walking improves locomotor function, which may be due to repeated activation of locomotor circuits and serotonin-dependent modulation of motor output. Separate studies in animals and individuals with spinal cord injury suggest acute intermittent hypoxia (AIH) can augment the effects of locomotor interventions through similar serotonin-dependent mechanisms, although no studies have coupled AIH with HIT in individuals poststroke. The goal of this study was to evaluate the safety and efficacy of AIH+HIT versus HIT alone in individuals with chronic stroke. METHODS: This phase II double-blind randomized, crossover trial recruited individuals between 18 and 85 years old, >6 months poststroke, and self-selected speeds <1.0 m/s. Participants received up to 15 sessions of AIH for 30 minutes using 15 cycles of hypoxia (60-90 seconds; 8%-9% O2) and normoxia (30-60 seconds; 21% O2), followed by 1 hour of HIT targeting >75% heart rate reserve. The control condition received normoxia for 30 minutes before HIT. Following the first training phase, participants performed the second phase >1 month later. The primary outcomes were self-selected speed and fastest speed, a 6-minute walk test, and peak treadmill speed. A 3-way mixed-model ANOVA assessed the effects of time, training, and order of interventions. RESULTS: Of 55 individuals screened, 35 were randomized to AIH+HIT or normoxia+HIT first, and 28 individuals completed both interventions, revealing greater gains in self-selected speeds (0.14 [0.08-0.18] versus 0.05 [0.01-0.10] m/s), fastest speed (0.16 [0.10-0.21] versus 0.06 [0.02-0.10] m/s), and peak treadmill speed (0.21 [0.14-0.29] versus 0.11 [0.06-0.16] m/s) following AIH+HIT versus normoxia+HIT (P<0.01) with no order effects. Greater gains in spatiotemporal symmetry were observed with AIH+HIT, with worse outcomes for those prescribed serotonin-mediated antidepressant medications. CONCLUSIONS: AIH+HIT resulted in greater gains in locomotor function than normoxia+HIT. Subsequent phase III trials should further evaluate the efficacy of this intervention. REGISTRATION: URL: https://clinicaltrials.gov/; Unique identifier: NCT04472442.

Comparative Efficacy of High-Intensity Training Versus Conventional Training in Individuals With Chronic Traumatic Brain Injury: A Pilot Randomized Controlled Study.

Numerous studies have evaluated the efficacy of interventions to improve locomotion after acute-onset brain injury, although most focus on patients with stroke, with less attention toward traumatic brain injury (TBI). For example, a number of studies in patients post-stroke have evaluated the effects of high-intensity training (HIT) attempting to maximize stepping practice, while no studies have attempted this intervention in patients with TBI. The purpose of this blinded-assessor randomized trial was to evaluate the effects of HIT focused on stepping practice versus conventional training on walking and secondary outcomes in individuals with TBI. Using a crossover design, ambulatory participants with TBI >6-months duration performed HIT focused on stepping in variable contexts (overground, treadmill, stairs) or conventional training for up to 15 sessions over five weeks, with interventions alternated >4 weeks later. HIT focused on maximizing stepping practice while trying to achieve higher cardiovascular intensities (>70% heart rate reserve), while conventional training focused on impairment-based and functional exercises with no restrictions on intensities achieved. Greater increases in 6-min walk test and peak treadmill speed during graded exercise testing were observed after HIT versus conventional training, with moderate associations between differences in stepping practice and outcomes. Greater gains were also observed in estimates of aerobic capacity and efficiency after HIT, with additional improvements in selected cognitive assessments. The present study suggests that the amount and intensity of stepping practice may be important determinants of improved locomotor outcomes in patients with chronic TBI, with possible secondary benefits on aerobic capacity/efficiency and cognition. Clinical Trial Registration-URL: https://clinicaltrials.gov/; Unique Identifier: NCT04503473.