Spinal Cord Injuries
Conditions
Keywords
acute intermittent hypoxia, breathing, spinal cord injury, motor function
Brief summary
This study will examine if acute intermittent hypoxia (brief episodes of breathing lower oxygen), which has been shown to enhance plasticity and motor output, can enhance functional outcomes and muscle activation in individuals with spinal cord injury. Our aim is to assess breathing, sitting, standing and walking functional ability before and after acute intermittent hypoxia, compared to a sham treatment. This information may be useful in advancing rehabilitation for people with spinal cord injuries.
Detailed description
Recent evidence has shown that acute intermittent hypoxia can strengthen motor pathways after spinal cord injury, and enhance walking outcomes after walking rehabilitation compared to walking rehabilitation alone. A single session of acute intermittent hypoxia has also been shown to temporarily enhance breathing and limb strength in people with spinal cord injury. Further evidence supports the hypothesis that acute intermittent hypoxia acts on all motor pathways, and thus can enhance the strength of most muscles in the body. Spinal cord injury affects the muscles that control respiration. Decreased respiratory muscle function can lead to diseases of the respiratory system, which are the primary cause of death and significant cause of re-hospitalization after spinal cord injury. Deficits in postural muscle function affect one's ability to balance, safely maintain a seated position, or ambulate after spinal cord injury, severely impacting daily activities such as self-care and feeding skills. This study will test the hypothesis that a single session of acute intermittent hypoxia will increase strength and activation of the muscles that control respiration and posture, leading to improved scores on functional assessments in individuals with chronic spinal cord injury. Our long term goal is to better understand the therapeutic potential of acute intermittent hypoxia combined with physical rehabilitation for individuals with chronic spinal cord injury.
Interventions
DEVICEHypoxia via Hypoxico Hyp-123
During acute intermittent hypoxia, subjects will undergo 15 brief exposures (60-120 seconds) of low oxygen air (9-15% inspired oxygen) delivered by an air generator, alternated with 15 brief exposures (60-120 seconds) of ambient room air.
DEVICESham via Hypoxico Hyp-123
During sham intermittent hypoxia, subjects will undergo 15 brief exposures (60-120 seconds) of normal oxygen air (21% inspired oxygen) delivered by an air generator, alternated with 15 brief exposures (60-120 seconds) of ambient room air.
Sponsors
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Subjects will be asked to participate in two visits at least 7 days apart. Subjects will be assessed on various clinical outcomes before and after an exposure to one of two treatments. In one visit, subjects will be assessed before and after acute intermittent hypoxia, consisting of brief exposures of breathing low oxygen air, alternated with brief exposures to room air. In the other visit, subjects will be assessed before and after an exposure to a sham treatment, consisting of breathing brief exposures of normal oxygen air, alternated with brief exposures to room air. Subjects will undergo acute intermittent hypoxia or a sham treatment in a randomized order.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, ages 18-65 2. Greater than 6 months post-spinal cord injury 3. Spinal cord injury affecting segments between C4-T12 4. No other known neurological disorders 5. Able to provide informed consent 6. no severe musculoskeletal impairments, open wounds, or skin lesions that would limit participation in functional assessments.
Exclusion criteria
1. Presence of a self-reported uncontrolled medical condition including, but not limited to: cardiovascular disease; sleep apnea; obstructive lung disease; severe neuropathic or chronic pain; severe recurrent autonomic dysreflexia 2. Severe, untreated bladder or urinary tract infection 3. Presence of severe musculoskeletal impairments, open wounds, or skin lesions that would limit participation in functional assessments 4. Women who report being pregnant or test positive on a pregnancy test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mouth Occlusion Pressure (P0.1) | Change between baseline and 30 minutes post-intermittent hypoxia or sham. | An assessment of the pressure generated in the first 0.1 seconds of the participant's initiation of inhalation. |
| Change in Maximal Inspiratory Pressure | Change between baseline and 30 minutes post-intermittent hypoxia or sham. | An assessment of inspiratory muscle strength. |
| Change in Maximal Expiratory Pressure | Change between baseline and 30 minutes post-intermittent hypoxia or sham. | An assessment of expiratory muscle strength. |
| Change in Forced Vital Capacity | Change between baseline and 30 minutes post-intermittent hypoxia or sham. | An assessment of how much air a person can forcefully exhale after a maximal inspiratory effort. |
Countries
United States
Participant flow
Recruitment details
Individuals were recruited through advertisements and rehabilitation health facilities in north Florida. Recruitment occurred from 07/2017 through 12/2019.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Subjects with chronic spinal cord injury completed a single session of acute intermittent hypoxia with low oxygen air (15 exposures of 60-120 seconds, 9-15% inspired oxygen, alternated with 60-120 seconds of room air) and a single session of sham acute intermittent hypoxia with room air (15 exposures of room air, 60-120 seconds, 21% oxygen). A washout of at least 7 days separated the two sessions. | 17 |
| Total | 17 |
Baseline characteristics
| Characteristic | All Study Participants | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 17 Participants | — |
| Age, Continuous | 34.1 years STANDARD_DEVIATION 14.5 | — |
| ASIA Impairment Scale AIS A Complete SCI | 6 Participants | — |
| ASIA Impairment Scale AIS B motor complete SCI | 7 Participants | — |
| ASIA Impairment Scale AIS C motor incomplete | 3 Participants | — |
| ASIA Impairment Scale AIS D motor incomplete | 1 Participants | — |
| Lower Extremity Motor Score (LEMS) | 4.6 units on a scale STANDARD_DEVIATION 12.4 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 17 participants | — |
| Sex: Female, Male Female | 4 Participants | — |
| Sex: Female, Male Male | 13 Participants | — |
| Spinal Cord Injury chronicity | 63.1 months STANDARD_DEVIATION 112.9 | — |
| Upper Extremity Motor Score (UEMS) | 40.2 units on a scale STANDARD_DEVIATION 15.3 | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 17 |
| other Total, other adverse events | 0 / 17 | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
Primary
Change in Forced Vital Capacity
An assessment of how much air a person can forcefully exhale after a maximal inspiratory effort.
Time frame: Change between baseline and 30 minutes post-intermittent hypoxia or sham.
Population: The measure was not obtained on 3 participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants - Acute Intermittent Hypoxia | Change in Forced Vital Capacity | -0.01 Liters | Standard Deviation 0.17 |
| All Study Participants - Sham | Change in Forced Vital Capacity | 0.00 Liters | Standard Deviation 0.21 |
p-value: <0.05ANOVA
Primary
Change in Maximal Expiratory Pressure
An assessment of expiratory muscle strength.
Time frame: Change between baseline and 30 minutes post-intermittent hypoxia or sham.
Population: All participants completed the measure and were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants - Acute Intermittent Hypoxia | Change in Maximal Expiratory Pressure | 4.3 cmH2O | Standard Deviation 11.5 |
| All Study Participants - Sham | Change in Maximal Expiratory Pressure | 2.9 cmH2O | Standard Deviation 9.8 |
p-value: <0.05Wilcoxon (Mann-Whitney)
Primary
Change in Maximal Inspiratory Pressure
An assessment of inspiratory muscle strength.
Time frame: Change between baseline and 30 minutes post-intermittent hypoxia or sham.
Population: All participants completed the measure and were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants - Acute Intermittent Hypoxia | Change in Maximal Inspiratory Pressure | 8.2 cmH2O | Standard Deviation 12.3 |
| All Study Participants - Sham | Change in Maximal Inspiratory Pressure | -3.0 cmH2O | Standard Deviation 11.3 |
p-value: <0.05Wilcoxon (Mann-Whitney)
Primary
Change in Mouth Occlusion Pressure (P0.1)
An assessment of the pressure generated in the first 0.1 seconds of the participant's initiation of inhalation.
Time frame: Change between baseline and 30 minutes post-intermittent hypoxia or sham.
Population: This measure was obtained in 12 participants. 12 participants were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants - Acute Intermittent Hypoxia | Change in Mouth Occlusion Pressure (P0.1) | 0.24 cmH2O | Standard Deviation 0.3 |
| All Study Participants - Sham | Change in Mouth Occlusion Pressure (P0.1) | 0.15 cmH2O | Standard Deviation 0.5 |
p-value: <0.05Wilcoxon (Mann-Whitney)