Effects of Breathing and Walking Treatments on Recovery Post-Spinal Cord Injury

Study Overview
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Brief Summary
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Change to Reflect What Was Done and reason Changes Were Made. The purpose of this study is to determine (1) if a specific breathing treatment (intermittent hypoxia) can promote changes in breathing function and (2) if pairing breathing treatments (hypoxia) with locomotor training can enhance the benefits of walking recovery observed with locomotor training alone (without breathing treatments).

Detailed Description
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Spinal cord injury (SCI) is a very disabling health problem. Paralysis and paresis of limb and trunk muscles are major consequences of SCI and result in the inability to walk or difficulty walking. The most commonly stated goal by individuals with SCI during rehabilitation is the desire to walk again. Locomotor training (LT) that uses a body-weight support system and treadmill (BWST) is a task-specific rehabilitation intervention that allows practice of walking at normal speeds while loading the lower extremities, facilitating upright posture, and hip extension. Substantial improvement in ambulation can occur following locomotor training (LT) in individuals with motor incomplete spinal cord injury (iSCI). Despite these advances in activity-dependent rehabilitation, a need exists for defining complementary strategies that further amplify endogenous neuroplasticity. The proposed study will assess the therapeutic potential of (1) a respiratory training intervention (acute intermittent hypoxia, or AIH) on breathing function and (2) a combined locomotor (LT) and respiratory (AIH) training intervention for enhancing walking recovery.

Official Title
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Intermittent Hypoxia and Locomotor Training: Effects Following SCI

Conditions
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Spinal Cord Injuries, Brown Sequard, Central Cord Syndrome

Intervention / Treatment
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* Other: Intermittent Hypoxia
* Other: Locomotor Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults at least 18 years of age At least 12 months post-incomplete spinal cord injury (I-SCI), including but not limited to the following syndromes: Brown Sequard and Central Cord Syndromes Upper motor neuron lesion (with upper motor neuron signs (i.e. presence of clonus, spasms, and/or hyperreflexia)) A diagnosis of first time SCI including etiology from trauma, vascular, or orthopedic pathology Resting oxygen saturation (SpO2) levels of 95-99% Individuals who ambulate independently, with an assistive device, or who can walk when provided manual assistance Persons using anti-spasticity medication must maintain stable medication dosage during the study Able to give informed consent. Medical approval by individual's physician Exclusion Criteria: Current participation in a rehabilitation program/research protocol that could interfere or influence the outcome measures of the current study History of congenital SCI (e.g. myelomeningocele, intraspinal neoplasm, Frederich's ataxia) or other degenerative spinal disorders (e.g. spinocerebellar degeneration, syringomyelia) that may complicate the protocol Inappropriate or unsafe fit of the harness due to the participant's body size and/or joint contractures or severe spasticity that would prohibit the safe provision of either training modality. Severe spasticity that would prohibit the safe provision of training. Pregnancy - all women of childbearing age will be required to undergo pregnancy testing prior to enrollment Unstable medical condition that could interfere with safety during participation in study (i.e. symptomatic cardiopulmonary complication, osteoporosis, contractures or other significant medical complications that would prohibit or interfere with testing of walking function and training or alter compliance with a training protocol)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1 Arm (Pilot)<br>Individuals were exposed to intermittent hypoxia and locomotor training to establish our interventions (set up lab, train personnel, develop study protocols/interventions, etc) | Other: Intermittent Hypoxia<br>* Individuals received exposure to intermittent hypoxia for 10 days, and placebo for 1-2 days.<br>* Other names: Breathing Treatment;Other: Locomotor Training<br>* Individuals received 10 days of locomotor training, intense walking training on a treadmill with body weight support. Manual assistance was provided at the legs to optimize stepping patterns.<br>|
| Experimental: Phase 2 Arm (LTF)<br>Individuals were exposed to 10 days of intermittent hypoxia to determine the effect of this intervention on ventilatory long-term facilitation, as measured by minute ventilation | Other: Intermittent Hypoxia<br>* Individuals received exposure to intermittent hypoxia for 10 days, and placebo for 1-2 days.<br>* Other names: Breathing Treatment;|
| Other: Phase 3 Arm (Ventilatory Loading)<br>Individuals were exposed to 10 days of intermittent hypoxia to determine changes in ventilatory loading. | Other: Intermittent Hypoxia<br>* Individuals received exposure to intermittent hypoxia for 10 days, and placebo for 1-2 days.<br>* Other names: Breathing Treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minute Ventilation - Phase 2 | Minute ventilation (Ve) is the volume of gas inhaled or exhaled from a person's lungs per minute. Minute ventilation during the end-recovery (ER) period at initial (i.e., Days 1 and 2, initial ER period) and final (i.e., Days 9 and 10, final ER period) days of the IH protocol were normalized to values from baseline with elevated carbon dioxide (B2) within each individual session to characterize daily effects of exposure to IH at the beginning and end of treatment. Values from baseline with elevated carbon dioxide and the ER period during the final days of the protocol (final B2 and final ER period, respectively) also were normalized to elevated carbon dioxide baseline during initial days of the protocol (initial B2) to describe the cumulative effects of repeated exposure to IH. Outcomes are reported as % increases in minute ventilation during initial and final treatment sessions for daily/acute effects and cumulative/chronic effects. | Pre- versus Post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilatory Loading - Phase 3 | Ventilatory load compensation was assessed in two ways. Mean slopes for (1) pressure vs. resistance (P vs R) and (2) airflow vs. resistance (AF vs R) were calculated for pre- and post-IH treatment. | Pre- versus Post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal cord injuries, Walking recovery, Respiration