Spinal Cord Diseases, Spinal Cord Injuries
Conditions
Keywords
Spinal Cord Injury, Stimulation, Spinal Stimulation, Noninvasive stimulation, Acute intermittent hypoxia, Hypoxia
Brief summary
This is a single blind, sham controlled crossover trial that will evaluate the effectiveness of acute intermittent hypoxia therapy (AIH) combined with transcutaneous (non-invasive) spinal cord stimulation on gait and balance function for individuals after spinal cord injury.
Detailed description
OBJECTIVES: * To determine whether acute intermittent hypoxia therapy (AIH) combined with transcutaneous spinal cord stimulation during ambulation training modulates spinal locomotor networks in individuals with spinal cord injury * To determine whether acute intermittent hypoxia therapy (AIH) combined with transcutaneous spinal cord stimulation during ambulation training improves locomotor function in individuals with spinal cord injury * To determine whether acute intermittent hypoxia therapy (AIH) combined with transcutaneous spinal cord stimulation during ambulation training improves symmetry of gait in individuals with spinal cord injury * To determine whether acute intermittent hypoxia therapy (AIH) combined with transcutaneous spinal cord stimulation during ambulation training improves standing posture and balance in individuals with spinal cord injury * To determine whether ambulation efficiency (improved cardiovascular conditioning) improves with a combination of AIH, transcutaneous spinal cord stimulation and ambulation training in individuals with spinal cord injury
Interventions
DEVICEAcute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training
Subjects will receive up to 45 minutes of AIH prior to receiving transcutaneous electrical spinal cord stimulation delivered by a Transcutaneous Spinal Cord Neurostimulator while performing locomotor activities.
OTHERSham Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training
Subjects will perform locomotor activities with transcutaneous electrical spinal cord stimulation after receiving sham acute intermittent hypoxia
OTHERSham Acute Intermittent Hypoxia + Sham Non Invasive Spinal Cord Stimulation + Gait Training
Subjects will perform locomotor activities with sham transcutaneous electrical spinal cord stimulation after receiving sham acute intermittent hypoxia
Sponsors
University of California, Los Angeles
Shirley Ryan AbilityLab
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants have been diagnosed with a spinal cord injury below level C2 * ASIA Impairment Scale Grade A-D * Participants are 18 years of age or older * Participants are at least 6 months post spinal cord injury * Participants with paraplegia or tetraplegia secondary to a single spinal cord injury * Participants are able to provide informed consent * Participants are not currently receiving regular physical therapy services
Exclusion criteria
* Individuals less than 18 years of age * Individuals less than 6 months post spinal cord injury * Individuals with ataxia * Individuals with multiple spinal cord injury history * Pregnancy or nursing * Pacemaker or anti-spasticity implantable pumps * Active pressure sores * Unhealed bone fractures * Peripheral neuropathies * Painful musculoskeletal dysfunction due to active injuries or infections * Severe contractures in the lower extremities * Active urinary tract infection * Clinically significant depression, psychiatric disorders, or ongoing drug abuse * Diagnosed with any of the following medical conditions: congestive heart failure, cardiac arrhythmias, uncontrolled hypertension, uncontrolled diabetes mellitus, chronic obstructive pulmonary disease, emphysema, severe asthma, previous myocardial infraction, or known carotid/intracerebral artery stenosis * Individuals with a tracheostomy or who utilize mechanical ventilation. * Individuals who are currently enrolled in another interventional research study or in therapy related to upper extremity function. * Participants will be excluded if they have had a botulinum toxin injection to lower extremity musculature within the last 3 months. Participants will need to refrain from lower extremity botulinum toxin injections for the duration of the study. If participants wean off antispasticity medications to successfully complete the responsiveness to AIH screening session, they will need to refrain from the medications for the duration of the study. * Documented sleep apnea. * Orthopedic injuries or surgeries that would impact an individual's ability to use the lower extremity. * Traumatic brain injury or other neurological conditions that would impact the study. * Blood hemoglobin levels less than 10g/dL. We will not include the following populations: * Adults unable to consent, unless accompanied by a legally authorized representative. * Individuals who are not yet adults (infants, children, teenagers) * Pregnant women * Prisoners
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 6 Minute Walk Test | Baseline (initial visit within an arm), Intervention session 5 within each arm (T5), 3 days after intervention sessions complete within each arm (POST), 1 week after intervention sessions are complete within each arm (1-week follow up) | The 6 Minute Walk Test (6MWT) measures the distance a subject can walk indoors on a flat, hard surface in a period of 6 minutes, using assertive devices, as necessary. The test is a reliable and valid evaluation of functional exercise capacity and is used as a sub-maximal test of aerobic capacity and endurance. The walk test is patient self-paced and assesses the level of functional capacity. Patients are allowed to stop and rest during the test, however, the timer does not stop. If the patient is unable to complete the time, the time stopped is noted and reason for stopping prematurely is recorded. This test was completed at 4 time points within each arm: 1) Baseline prior to starting each arm, 2) intervention session 5 within each arm (T5), 3) 3 days after the intervention sessions were complete for the given arm (POST), and 4) 1 week after all intervention sessions were complete for a given arm (1-week follow up) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 10 Meter Walk Test, Fast Velocity | Baseline (initial visit within an arm), Intervention session 5 within each arm (T5), 3 days after intervention sessions complete within each arm (POST), 1 week after intervention sessions are complete within each arm (1-week follow up) | This test will examine the patient's gait speed. Patients will be directed to walk at their preferred maximum but safe speed: 1) Baseline prior to starting each arm, 2) intervention session 5 within each arm (T5), 3) 3 days after the intervention sessions were complete for the given arm (POST), and 4) 1 week after all intervention sessions were complete for a given arm (1-week follow up) |
| Timed Up and Go Test: Assesses Mobility, Balance, Walking Ability and Fall Risk | Baseline (initial visit within an arm), Intervention session 5 within each arm (T5), 3 days after intervention sessions complete within each arm (POST), 1 week after intervention sessions are complete within each arm (1-week follow up) | The participant starts seated in a chair with his/her back against the chair back. On command, the participant rises from the chair, walks 3 meters, turns, walks back to the chair and sits down. Timing begins when the command to start is given and stops when the participant returns to a seated position. 1) Baseline prior to starting each arm, 2) intervention session 5 within each arm (T5), 3) 3 days after the intervention sessions were complete for the given arm (POST), and 4) 1 week after all intervention sessions were complete for a given arm (1-week follow up) |
Countries
United States
Participant flow
Pre-assignment details
All participants completed all arms of the study. The order of arm completion was randomly assigned using a block style approach.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All participants completed 3 arms of the study, in a random order: 1) Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training, 2) Sham Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training, 3) Sham Acute Intermittent Hypoxia + Sham Non Invasive Spinal Cord Stimulation + Gait Training | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 46.90 years STANDARD_DEVIATION 16.53 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Gait Speed as measured by the 10-meter walk test (10MWT) at self-selected velocity (SSV | 0.63 meters per second (m/s) STANDARD_DEVIATION 0.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 10 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Change in 6 Minute Walk Test
The 6 Minute Walk Test (6MWT) measures the distance a subject can walk indoors on a flat, hard surface in a period of 6 minutes, using assertive devices, as necessary. The test is a reliable and valid evaluation of functional exercise capacity and is used as a sub-maximal test of aerobic capacity and endurance. The walk test is patient self-paced and assesses the level of functional capacity. Patients are allowed to stop and rest during the test, however, the timer does not stop. If the patient is unable to complete the time, the time stopped is noted and reason for stopping prematurely is recorded. This test was completed at 4 time points within each arm: 1) Baseline prior to starting each arm, 2) intervention session 5 within each arm (T5), 3) 3 days after the intervention sessions were complete for the given arm (POST), and 4) 1 week after all intervention sessions were complete for a given arm (1-week follow up)
Time frame: Baseline (initial visit within an arm), Intervention session 5 within each arm (T5), 3 days after intervention sessions complete within each arm (POST), 1 week after intervention sessions are complete within each arm (1-week follow up)
Population: 10 participants completed and analyzed. 1 was dropped from analysis as an outlier (difference of greater than 1.5\*IQR (interquartile range) for all gait outcomes) = 9 participants in analysis total.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Change in 6 Minute Walk Test | Baseline to 1-week follow up (17-19 days after baseline from stated arm) | 21.80 meters (m) |
| Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Change in 6 Minute Walk Test | Baseline to T5 (7-8 days after baseline from stated arm) | 19.57 meters (m) |
| Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Change in 6 Minute Walk Test | Baseline to POST (10-11 days after baseline from stated arm) | 19.03 meters (m) |
| Sham Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Change in 6 Minute Walk Test | Baseline to POST (10-11 days after baseline from stated arm) | 12.01 meters (m) |
| Sham Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Change in 6 Minute Walk Test | Baseline to 1-week follow up (17-19 days after baseline from stated arm) | 10.33 meters (m) |
| Sham Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Change in 6 Minute Walk Test | Baseline to T5 (7-8 days after baseline from stated arm) | 12.28 meters (m) |
| Sham Acute Intermittent Hypoxia + Sham Non Invasive Spinal Cord Stimulation + Gait Training | Change in 6 Minute Walk Test | Baseline to T5 (7-8 days after baseline from stated arm) | 9.63 meters (m) |
| Sham Acute Intermittent Hypoxia + Sham Non Invasive Spinal Cord Stimulation + Gait Training | Change in 6 Minute Walk Test | Baseline to 1-week follow up (17-19 days after baseline from stated arm) | 16.13 meters (m) |
| Sham Acute Intermittent Hypoxia + Sham Non Invasive Spinal Cord Stimulation + Gait Training | Change in 6 Minute Walk Test | Baseline to POST (10-11 days after baseline from stated arm) | 15.63 meters (m) |
Secondary
Change in 10 Meter Walk Test, Fast Velocity
This test will examine the patient's gait speed. Patients will be directed to walk at their preferred maximum but safe speed: 1) Baseline prior to starting each arm, 2) intervention session 5 within each arm (T5), 3) 3 days after the intervention sessions were complete for the given arm (POST), and 4) 1 week after all intervention sessions were complete for a given arm (1-week follow up)
Time frame: Baseline (initial visit within an arm), Intervention session 5 within each arm (T5), 3 days after intervention sessions complete within each arm (POST), 1 week after intervention sessions are complete within each arm (1-week follow up)
Population: 14 participants enrolled. 4 dropped out of the study due to personal or transportation reasons; therefore, 10 participants completed and analyzed. 1 was dropped from analysis as an outlier (difference of greater than 1.5\*IQR (interquartile range) for all gait outcomes) = 9 participants in analysis total.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Change in 10 Meter Walk Test, Fast Velocity | Baseline to POST (10-11 days after baseline from stated arm) | 0.05 meters per second |
| Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Change in 10 Meter Walk Test, Fast Velocity | Baseline to T5 (7-8 days after baseline from stated arm) | 0.03 meters per second |
| Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Change in 10 Meter Walk Test, Fast Velocity | Baseline to 1-week follow up (17-19 days after baseline from stated arm) | 0.03 meters per second |
| Sham Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Change in 10 Meter Walk Test, Fast Velocity | Baseline to POST (10-11 days after baseline from stated arm) | -0.01 meters per second |
| Sham Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Change in 10 Meter Walk Test, Fast Velocity | Baseline to T5 (7-8 days after baseline from stated arm) | 0.00 meters per second |
| Sham Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Change in 10 Meter Walk Test, Fast Velocity | Baseline to 1-week follow up (17-19 days after baseline from stated arm) | 0.01 meters per second |
| Sham Acute Intermittent Hypoxia + Sham Non Invasive Spinal Cord Stimulation + Gait Training | Change in 10 Meter Walk Test, Fast Velocity | Baseline to T5 (7-8 days after baseline from stated arm) | 0.04 meters per second |
| Sham Acute Intermittent Hypoxia + Sham Non Invasive Spinal Cord Stimulation + Gait Training | Change in 10 Meter Walk Test, Fast Velocity | Baseline to 1-week follow up (17-19 days after baseline from stated arm) | -0.01 meters per second |
| Sham Acute Intermittent Hypoxia + Sham Non Invasive Spinal Cord Stimulation + Gait Training | Change in 10 Meter Walk Test, Fast Velocity | Baseline to POST (10-11 days after baseline from stated arm) | 0.02 meters per second |
Secondary
Timed Up and Go Test: Assesses Mobility, Balance, Walking Ability and Fall Risk
The participant starts seated in a chair with his/her back against the chair back. On command, the participant rises from the chair, walks 3 meters, turns, walks back to the chair and sits down. Timing begins when the command to start is given and stops when the participant returns to a seated position. 1) Baseline prior to starting each arm, 2) intervention session 5 within each arm (T5), 3) 3 days after the intervention sessions were complete for the given arm (POST), and 4) 1 week after all intervention sessions were complete for a given arm (1-week follow up)
Time frame: Baseline (initial visit within an arm), Intervention session 5 within each arm (T5), 3 days after intervention sessions complete within each arm (POST), 1 week after intervention sessions are complete within each arm (1-week follow up)
Population: 14 participants enrolled. 4 dropped out of the study due to personal or transportation reasons; therefore, 10 participants completed and analyzed. 1 was dropped from analysis as an outlier (difference of greater than 1.5\*IQR (interquartile range) for all gait outcomes) = 9 participants in analysis total.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Timed Up and Go Test: Assesses Mobility, Balance, Walking Ability and Fall Risk | Baseline to POST (10-11 days after baseline from stated arm) | 3.39 seconds |
| Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Timed Up and Go Test: Assesses Mobility, Balance, Walking Ability and Fall Risk | Baseline to T5 (7-8 days after baseline from stated arm) | 2.67 seconds |
| Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Timed Up and Go Test: Assesses Mobility, Balance, Walking Ability and Fall Risk | Baseline to 1-week follow up (17-19 days after baseline from stated arm) | 3.49 seconds |
| Sham Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Timed Up and Go Test: Assesses Mobility, Balance, Walking Ability and Fall Risk | Baseline to POST (10-11 days after baseline from stated arm) | -0.06 seconds |
| Sham Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Timed Up and Go Test: Assesses Mobility, Balance, Walking Ability and Fall Risk | Baseline to T5 (7-8 days after baseline from stated arm) | 1.45 seconds |
| Sham Acute Intermittent Hypoxia + Non Invasive Spinal Cord Stimulation + Gait Training | Timed Up and Go Test: Assesses Mobility, Balance, Walking Ability and Fall Risk | Baseline to 1-week follow up (17-19 days after baseline from stated arm) | 0.78 seconds |
| Sham Acute Intermittent Hypoxia + Sham Non Invasive Spinal Cord Stimulation + Gait Training | Timed Up and Go Test: Assesses Mobility, Balance, Walking Ability and Fall Risk | Baseline to T5 (7-8 days after baseline from stated arm) | 1.00 seconds |
| Sham Acute Intermittent Hypoxia + Sham Non Invasive Spinal Cord Stimulation + Gait Training | Timed Up and Go Test: Assesses Mobility, Balance, Walking Ability and Fall Risk | Baseline to 1-week follow up (17-19 days after baseline from stated arm) | 0.19 seconds |
| Sham Acute Intermittent Hypoxia + Sham Non Invasive Spinal Cord Stimulation + Gait Training | Timed Up and Go Test: Assesses Mobility, Balance, Walking Ability and Fall Risk | Baseline to POST (10-11 days after baseline from stated arm) | 0.73 seconds |