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

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. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02632422 . Registered 16 December 2015.

Comparison of Resistance-Based Walking Cardiorespiratory Test to the Bruce Protocol.

Hurt, CP, Bamman, M, Naidu, A, and Brown, DA. Comparison of resistance-based walking cardiorespiratory test to the Bruce Protocol. J Strength Cond Res 34(12): 3569-3576, 2020-Cardiorespiratory fitness is assessed through graded exercise tests that determine the maximum amount of sustained mechanical work that an individual can perform while also providing health- and fitness-related information. This article describes a novel method to perform graded exercise tests that use posteriorly directed resistive forces. The purpose of this investigation was to validate a novel resistance-based test (RBT) in comparison with a traditional speed- and incline-based test (SIBT) in a cohort of nonimpaired individuals. Twenty nonimpaired individuals, 8 men and 20 women age 28.4 ± 9.6, range 20-54 years old performed 2 maximal exercise tests. The SIBT used the Bruce Protocol and increased treadmill incline and speed every 3 minutes. The RBT used a robotic device interfaced with the treadmill that provided specified horizontal resistive forces at the center of mass calculated to match each Bruce Protocol stage while individuals walked at 1.1 m·s. Subjects obtained ∼3% higher maximum V[Combining Dot Above]O2 measure using the speed- and incline-based method (dependent t-test p = 0.08). V[Combining Dot Above]O2peaks between tests were strongly correlated (r = 0.93, p < 0.001). Peak values of secondary physiologic measures (i.e., max heart rate and respiratory exchange ratio) were within 3% between tests. We found a significant linear relationship between mass-specific work rate and measured V[Combining Dot Above]O2 stage by stage for both tests, but no significant difference between each linear fit (p = 0.84). These data suggest that horizontal resistive forces, while walking on a treadmill, can be used to increase aerobic effort in a way that closely simulates work rates of the Bruce Protocol.

Fore-aft resistance applied at the center of mass using a novel robotic interface proportionately increases propulsive force generation in healthy nonimpaired individuals walking at a constant speed.

BACKGROUND: Past studies have utilized external interfaces like resistive bands and motor-generated pulling systems to increase limb propulsion during walking on a motorized treadmill. However, assessing changes in limb propulsion against increasing resistance demands during self-controlled walking has not been undertaken. PURPOSE: We assessed limb propulsion against increasing fore-aft loading demands by applying graded fore-aft (FA) resistance at the center of mass during walking in a novel, intent-driven treadmill environment that allowed participants to control their walking speeds. We hypothesized that to maintain a target speed against progressively increasing resistance, participants would proportionately increase their limb propulsion without increasing vertical force production, with accompanying increases in trailing limb angle and positive joint work. METHODS: Seventeen healthy-nonimpaired participants (mean age 52 yrs., SD = 11) walked at a target, self-controlled speed of 1.0 m/s against 10, 15, 20, and 25% (% body weight) FA resistance levels. We primarily assessed linear slope values across FA resistance levels for mean propulsive force and impulse and vertical impulse of the dominant limb using one-sample t-tests. We further assessed changes in trailing and leading limb angles and joint work using one-way ANOVAs. RESULTS: Participants maintained their target velocity within an a priori defined acceptable range of 1.0 m/s ± 0.2. They significantly increased propulsion proportional to FA resistance (propulsive force mean slope = 2.45, SD = 0.7, t (16) =14.44, p < 0.01; and propulsive impulse mean slope = 0.7, SD = 0.25, t (16) = 11.84, p < 0.01), but had no changes in vertical impulse (mean slope = - 0.04, SD =0.17, p > 0.05) across FA resistance levels. Mean trailing limb angle increased from 24.3° at 10% resistance to 27.4° at 25% (p < 0.05); leading limb angle decreased from - 18.4° to - 12.6° (p < 0.05). We also observed increases in total positive limb work (F (1.7, 26) = 16.88, p ≤ 0.001, η2 = 0.5), primarily attributed to the hip and ankle joints. CONCLUSIONS: FA resistance applied during self-driven walking resulted in increased propulsive-force output of healthy-nonimpaired individuals with accompanying biomechanical changes that facilitated greater limb propulsion. Future rehabilitation interventions for neurological populations may be able to utilize this principle to design task-specific interventions like progressive strength training and workload manipulation during aerobic training for improving walking function.

Daily acute intermittent hypoxia combined with walking practice enhances walking performance but not intralimb motor coordination in persons with chronic incomplete spinal cord injury.

Persons living with incomplete spinal cord injuries (SCI) often struggle to regain independent walking due to deficits in walking mechanics. They often dedicate many weeks of gait training before benefits to emerge, with additional training needed for benefits to persist. Recent studies in humans with SCI found that daily bouts of breathing low oxygen (acute intermittent hypoxia, AIH) prior to locomotor training elicited persistent (weeks) improvement in overground walking speed and endurance. AIH-induced improvements in overground walking may result from changes in control strategies that also enhance intralimb coordination; however, this possibility remains untested. Here, we examined the extent to which daily AIH combined with walking practice (AIH + WALK) improved overground walking performance and intralimb motor coordination in persons with chronic, incomplete SCI. METHODS: We recruited 11 persons with chronic (> 1 year), incomplete SCI to participate in a randomized, double-blind, balanced, crossover study. Participants first received either daily (5 consecutive days) AIH (15, 90-s episodes of 10.0% O2 with 60s intervals at 20.9% O2) or SHAM (15, 90s episodes at 20.9% O2 with 60s intervals at 20.9% O2) followed by 30-min of overground walking practice. They received the second treatment after a minimum 2-week washout period. We quantified overground walking performance, in terms of speed and endurance, using the 10-Meter Walk Test (10MWT) and 6-Minute Walk Test (6MWT), respectively. We quantified intralimb motor coordination using kinematic variability measures of foot trajectory (i.e., endpoint variability, EV) and of inter-joint coupling between the hip and knee, as well as between the knee and ankle joints (i.e., angular coefficient of correspondence, ACC). We compared the changes in walking performance relative to baseline (BL) between daily AIH + WALK and daily SHAM+WALK on treatment day 5 (T5), 1-week follow-up (F1), and 2-weeks follow-up (F2). We also compared these changes between participants who used bilateral walking aids (N = 5) and those who did not. To assess the effects of daily AIH + WALK on intralimb coordination, we compared potential treatment-induced changes in EV and ACC relative to BL at F1 and F2. RESULTS: Participants improved overground walking performance (speed and endurance) after daily AIH + WALK, but not SHAM+WALK. Following daily AIH + WALK, participants decreased their 10MWT time at T5 by 28% (95% CI 0.2-10.1 s, p = 0.04), F1 by 28% (95% CI 1.1-13.5 s, p = 0.01), and F2 by 27% (95% CI 1.4-13.9 s, p = 0.01) relative to BL. The greatest decreases in the 10MWT occurred in participants who used bilateral walking aids (p < 0.05). We also found daily AIH + WALK resulted in an increase in 6MWT distance at T5 by 22% (95% CI 13.3-72.6 m, p = 0.001), F1 by 21% (95% CI 13.1-72.5 m, p = 0.001), and F2 by 16% (95% CI 2.9-62.2 m, p = 0.02). However, measures of EV and ACC during self-selected walking conditions did not change following daily AIH + WALK (all p-values >0.50). CONCLUSIONS: Consistent with prior studies, daily AIH + WALK triggered improvements in walking speed and endurance that persisted for weeks after treatment. Greatest improvements in speed occurred in participants who used bilateral walking aids. No change in EV and ACC may suggest that intralimb motor coordination was not a significant gait training priority during daily AIH + WALK.

A Challenge-Based Approach to Body Weight-Supported Treadmill Training Poststroke: Protocol for a Randomized Controlled Trial.

BACKGROUND: Body weight support treadmill training protocols in conjunction with other modalities are commonly used to improve poststroke balance and walking function. However, typical body weight support paradigms tend to use consistently stable balance conditions, often with handrail support and or manual assistance. OBJECTIVE: In this paper, we describe our study protocol, which involved 2 unique body weight support treadmill training paradigms of similar training intensity that integrated dynamic balance challenges to help improve ambulatory function post stroke. The first paradigm emphasized walking without any handrails or manual assistance, that is, hands-free walking, and served as the control group, whereas the second paradigm incorporated practicing 9 essential challenging mobility skills, akin to environmental barriers encountered during community ambulation along with hands-free walking (ie hands-free + challenge walking). METHODS: We recruited individuals with chronic poststroke hemiparesis and randomized them to either group. Participants trained for 6 weeks on a self-driven, robotic treadmill interface that provided body weight support and a safe gait-training environment. We assessed participants at pre-, mid- and post 6 weeks of intervention-training, with a 6-month follow-up. We hypothesized greater walking improvements in the hands-free + challenge walking group following training because of increased practice opportunity of essential mobility skills along with hands-free walking. RESULTS: We assessed 77 individuals with chronic hemiparesis, and enrolled and randomized 30 individuals poststroke for our study (hands-free group=19 and hands-free + challenge walking group=20) from June 2012 to January 2015. Data collection along with 6-month follow-up continued until January 2016. Our primary outcome measure is change in comfortable walking speed from pre to post intervention for each group. We will also assess feasibility, adherence, postintervention efficacy, and changes in various exploratory secondary outcome measures. Additionally, we will also assess participant responses to a study survey, conducted at the end of training week, to gauge each group's training experiences. CONCLUSIONS: Our treadmill training paradigms, and study protocol represent advances in standardized approaches to selecting body weight support levels without the necessity for using handrails or manual assistance, while progressively providing dynamic challenges for improving poststroke ambulatory function during rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02787759; https://clinicaltrials.gov/ct2/show/NCT02787759 (Archived by Webcite at http://www.webcitation.org/6yJZCrIea).