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.

Increasing the Amount and Intensity of Stepping Training During Inpatient Stroke Rehabilitation Improves Locomotor and Non-Locomotor Outcomes.

BACKGROUND: The efficacy of traditional rehabilitation interventions to improve locomotion post-stroke, including providing multiple exercises targeting impairments and activity limitations, is uncertain. Emerging evidence rather suggests attempts to prioritize stepping practice at higher cardiovascular intensities may facilitate greater locomotor outcomes. OBJECTIVE: The present study was designed to evaluate the comparative effectiveness of high-intensity training (HIT) to usual care during inpatient rehabilitation post-stroke. METHODS: Changes in stepping activity and functional outcomes were compared over 9 months during usual-care (n = 131 patients < 2 months post-stroke), during an 18-month transition phase with attempts to implement HIT (n = 317), and over 12 months following HIT implementation (n = 208). The transition phase began with didactic and hands-on education, and continued with meetings, mentoring, and audit and feedback. Fidelity metrics included percentage of sessions prioritizing gait interventions and documenting intensity. Demographics, training measures, and outcomes were compared across phases using linear or logistic regression analysis, Kruskal-Wallis tests, or χ2 analysis. RESULTS: Across all phases, admission scores were similar except for balance (usual-care>HIT; P < .02). Efforts to prioritize stepping and achieve targeted intensities during HIT vs transition or usual-care phases led to increased steps/day (P < .01). During HIT, gains in 10-m walk [HIT median = 0.13 m/s (interquartile range: 0-0.35) vs usual-care = 0.07 m/s (0-0.24), P = .01] and 6-min walk [50 (9.3-116) vs 2.1 (0-56) m, P < .01] were observed, with additional improvements in transfers and stair-climbing. CONCLUSIONS: Greater efforts to prioritize walking and reach higher intensities during HIT led to increased steps/day, resulting in greater gains in locomotor and non-locomotor outcomes.

Gains in Daily Stepping Activity in People With Chronic Stroke After High-Intensity Gait Training in Variable Contexts.

OBJECTIVE: Many physical therapist interventions provided to individuals with chronic stroke can lead to gains in gait speed or endurance (eg, 6-Minute Walk Test [6MWT]), although changes in objective measures of participation are not often observed. The goal of this study was to determine the influence of different walking interventions on daily stepping (steps per day) and the contributions of demographic, training, and clinical measures to these changes. METHODS: In this secondary analysis of a randomized clinical trial, steps per day at baseline and changes in steps per day following 1 of 3 locomotor interventions were evaluated in individuals who were ambulatory and >6 months after stroke. Data were collected on 58 individuals who received ≤30 sessions of high-intensity training (HIT) in variable contexts (eg, tasks and environments; n = 19), HIT focused on forward walking (n = 19), or low-intensity variable training (n = 20). Primary outcomes were steps per day at baseline, at post-training, and at a 3-month follow-up, and secondary outcomes were gait speed, 6MWT, balance, and balance confidence. Correlation and regression analyses identified demographic and clinical variables associated with steps per day. RESULTS: Gains in steps per day were observed across all groups combined, with no between-group differences; post hoc within-group analyses revealed significant gains only following HIT in variable contexts. Both HIT groups showed gains in endurance (6MWT), with increases in balance confidence only following HIT in variable contexts. Changes in steps per day were associated primarily with gains in 6MWT, with additional associations with baseline 6MWT, lower-extremity Fugl-Meyer scores, and changes in balance confidence. CONCLUSION: HIT in variable contexts elicited gains in daily stepping, with changes primarily associated with gains in gait endurance. IMPACT: Providing HIT in variable contexts appears to improve measures of participation (eg, daily stepping) that may be associated with clinical measures of function. Gains in multiple measures of mobility and participation with HIT in variable contexts may improve the efficiency and value of physical therapy services.

Task-Specific Versus Impairment-Based Training on Locomotor Performance in Individuals With Chronic Spinal Cord Injury: A Randomized Crossover Study.

Background. Many research studies attempting to improve locomotor function following motor incomplete spinal cord injury (iSCI) focus on providing stepping practice. However, observational studies of physical therapy strategies suggest the amount of stepping practice during clinical rehabilitation is limited; rather, many interventions focus on mitigating impairments underlying walking dysfunction. Objective. The purpose of this blinded-assessor randomized trial was to evaluate the effects of task-specific versus impairment-based interventions on walking outcomes in individuals with iSCI. Methods. Using a crossover design, ambulatory participants with iSCI >1-year duration performed either task-specific (upright stepping) or impairment-based training for up to 20 sessions over ≤6 weeks, with interventions alternated after >4 weeks delay. Both strategies focused on achieving higher cardiovascular intensities, with training specificity manipulated by practicing only stepping practice in variable contexts or practicing tasks targeting impairments underlying locomotor dysfunction (strengthening, balance tasks, and recumbent stepping). Results. Significantly greater increases in fastest overground and treadmill walking speeds were observed following task-specific versus impairment-based training, with moderate associations between differences in amount of practice and outcomes. Gains in balance confidence were also observed following task-specific vs impairment-based training, although incidence of falls was also increased with the former protocol. Limited gains were observed with impairment-based training except for peak power during recumbent stepping tests. Conclusion. The present study reinforces work from other patient populations that the specificity of task practice is a critical determinant of locomotor outcomes and suggest impairment-based exercises may not translate to improvements in functional tasks. Clinical Trial Registration URL. https://clinicaltrials.gov/ ; Unique Identifier: NCT02115685.