The purpose of this study is to determine how combining bouts of low oxygen, transcutaneous spinal cord stimulation, and walking training may improve walking function for people with chronic spinal cord injury of different age groups.
The goal of the study is to determine the optimal dosage for different age groups of repeatedly breathing mild bouts of low oxygen for brief periods (termed acute intermittent hypoxia (AIH)) combined with transcutaneous spinal cord stimulation (tSTIM) to improve recovery of walking and strength after spinal cord injury. Preliminary studies have shown that combining AIH and tSTIM with walking training can enhance individuals walking training greater than just AIH or tSTIM. By using low oxygen as a pre-treatment to tSTIM during walking training, functional independence and quality of life may improve. Despite exciting preliminary results supporting the efficacy of AIH and tSTIM to enhance walking recovery after SCI, understanding factors that may enhance or undermine treatment responsiveness is warranted. Factors include establishing the role of age and sex dependency on appropriate dosing (number of sessions) AIH to provide the greatest plasticity-promoting effects on walking recovery for our aging population of persons living with SCI.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
60
Each participant will be exposed to 16 sessions of daily acute intermittent hypoxia via air generators over the span of four weeks. The generator will fill reservoir bags attached to a non-rebreathing facemask. Each session will consist of 15 episodes which include intervals of 1.5 minute hypoxia (FIO2=0.10±0.02, i.e. 10% O2) and 1 minute normoxia (FIO2=0.21±0.02).
Individuals will participate in 45 minutes of gait training while having transcutaneous spinal cord stimulation. Stimulation intensity will be 80% involuntary motor threshold.
Brooks Rehabilitation Hospital
Jacksonville, Florida, United States
RECRUITINGSpaulding Rehabilitation Hospital
Cambridge, Massachusetts, United States
RECRUITINGChange in walking recovery, assessed by 10 meter walk test (10MWT)
Participants walk ten meters without assistance at their fastest, but safest speed with a minimum of 1-minute of rest between two trials. Average speed across the up to three 10MWT trials will be used for analysis. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Time frame: Through study completion, an average of 14 weeks
Rate of change in walking recovery, assessed by 10 meter walk test (10MWT)
Participants walk ten meters without assistance at their fastest, but safest speed with a minimum of 1-minute of rest between two trials. Average speed across the up to three 10MWT trials will be used for analysis. Rate of change is the number of treatment sessions required to achieve an increase in 10MWT speed of at least the minimal clinically important difference (0.06 m/s) as compared to pre-treatment baseline.
Time frame: Through study completion, an average of 14 weeks
Change in walking recovery, assessed by 6 minute walk test (6MWT)
Participants perform the 6MWT at their fastest, most comfortable walking speed sustainable for 6 minutes. Distances will be recorded at 2 and 6 minutes. The test will be based upon the participant's ability to finish each assessment without human assistance. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Time frame: Through study completion, an average of 14 weeks
Change in walking recovery, assessed by timed up-and-go (TUG) test
The TUG test is used to assess the dynamic balance of an individual. It measures the amount of time (recorded in seconds) it takes for the individual to rise from a standard arm chair, walk a distance of 3 meters and return to the initial position resting against the back of the chair. Participants will perform up to three trials of the TUG test. Average speed across TUG trials will be used for analysis. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline
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Time frame: Through study completion, an average of 14 weeks
Change in pain severity, assessed by the Numeric Pain Rating Scale (NPRS)
Participants will report their pain level using the Numeric Pain Rating Scale. The scale is from 0 to 10; 0 being no pain and 10 being extreme pain. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Time frame: Through study completion, an average of 14 weeks
Change in cognitive function, assessed by the California Verbal Learning Test (CVLT)
The CVLT is a brief, individually administered battery to measure cognitive decline or improvement and assesses verbal learning and memory for older adolescents and adults. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Time frame: Through treatment completion, an average of 6 weeks
Counts of hypertensive events
Participants will have their systolic and diastolic blood pressure measured. A systemic hypertensive event is quantified as a systolic pressure exceeding 140 mmHg and/or diastolic pressure exceeding 90 mmHg.
Time frame: Through treatment completion, an average of 6 weeks
Counts of blood pressure measurements
Participants will have their systolic and diastolic blood pressure measured. Person-time is in units of person-measures (the sum of the total number of BP measurements) taken for each person. Person-measures accounts for the total number of chances for detecting a hypertensive event and accounts for measurements not made due to drop-out or a disqualifying adverse event.
Time frame: Through treatment completion, an average of 6 weeks
Systemic hypertension incidence rate
Participants will have their systolic and diastolic blood pressure measured. A systemic hypertensive event is quantified as a systolic pressure exceeding 140 mmHg and/or diastolic pressure exceeding 90 mmHg. A hypertension incident rate is the number of hypertensive events divided by the total person-time. Person-time is in units of person-measures (the sum of the total number of BP measurements) taken for each person. Person-measures accounts for the total number of chances for detecting a hypertensive event and accounts for measurements not made due to drop-out or a disqualifying adverse event.
Time frame: Through treatment completion, an average of 6 weeks
Number of autonomic dysreflexia events
The occurrence of autonomic dysreflexia will be assessed. An autonomic dysreflexia event will constitute a participant meeting: A. Either blood pressure criteria: 1. SBP increase from baseline of 20 mmHg not associated with exercise 2. SBP greater than 150 mmHg B. And any of the following symptoms: 1. Headache 2. Diaphoresis 3. Blurred vision
Time frame: Through treatment completion, an average of 6 weeks
Total person-time for autonomic dysreflexia
We define person-time in units of person-days (the number of days a person remains in the study). Person-days account for the total number of chances for detecting autonomic dysreflexia and accounts for days on which measurements were not made due to drop-out or a disqualifying adverse event.
Time frame: Through treatment completion, an average of 6 weeks
Autonomic dysreflexia incidence rate
The occurrence of autonomic dysreflexia will be assessed. An autonomic dysreflexia event will constitute a participant having a SBP increase from baseline of 20 mmHg not associated with exercise or systolic blood pressure (SBP) greater than 150 mmHg with complaints of headache, diaphoresis, and/or blurred vision and will be diagnosed by our study team clinicians. We will compute autonomic dysreflexia incident rate as the number of autonomic dysreflexia events divided by the total person-time. We define person-time in units of person-days (the number of days a person remains in the study). Person-days account for the total number of chances for detecting autonomic dysreflexia and accounts for days on which measurements were not made due to drop-out or a disqualifying adverse event.
Time frame: Through treatment completion, an average of 6 weeks
Change in lower extremity strength, assessed by American Spinal Injury Association Impairment Scale (AIS) lower extremity motor scores (LEMS)
The LEMS uses ASIA key muscles in both the lower extremities, with a total possible score of 50 (maximum score of 5 for each muscle group). Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Time frame: Through study completion, an average of 14 weeks
Change in spasticity, assessed by the Spinal Cord Assessment Tool for Spastic Reflexes (SCATS)
The study team will quantify the total lower extremity spasticity score using the cumulative sum of 3 SCATS subscales: clonus (0=no spasticity; 3=severe), flexor (0=no spasticity; 3=severe), and extensor (0=no spasticity; 3=severe). Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Time frame: Through study completion, an average of 14 weeks
Change in bowel dysfunction, assessed by the Neurogenic Bowel Dysfunction Score (NBDS) v2.1
This questionnaire is a symptom-based score for neurogenic bowel dysfunction. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Time frame: Through study completion, an average of 14 weeks
Change in bladder dysfunction, assessed by the Neurogenic Bladder Symptom Score (NBSS)
This questionnaire is a symptom-based score for neurogenic bladder dysfunction. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Time frame: Through study completion, an average of 14 weeks
Change in walking ability and assistive device use, assessed by Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI).
The SCI-FAI assesses functional walking ability in ambulatory individuals with SCI. Component scores range from 0 to 20 in the gait parameter component, 0 to 14 in the assistive device component, and 0 to 5 in the walking mobility component. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Time frame: Through study completion, an average of 14 weeks
Change in physical assistance needed, assessed by Walking Index for Spinal Cord Injury (WISCI) II
The WISCI is used to assess the amount of physical assistance is needed as well as devices required for walking following paralysis. This assessment is from 0-20 with value corresponding to a physical assistance description. Change is the difference between the post-treatment assessment 2 and pre-treatment baseline.
Time frame: Through study completion, an average of 14 weeks
Change in breathing function, assessed by FVC
Forced vital capacity will be measured, which is the volume of air forcibly expired after a maximal inspiration.
Time frame: Through study completion, an average of 14 weeks
Change in apnea hypopnea index
Time frame: Through treatment completion, an average of 6 weeks