Spinal Cord Injuries
Conditions
Keywords
Walk, Rehabilitation, Strength, Movement, Low oxygen, Electrical stimulation, Gait training
Brief summary
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.
Detailed description
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.
Interventions
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).
DEVICEWalking + tSTIM
Individuals will participate in 45 minutes of gait training while having transcutaneous spinal cord stimulation. Stimulation intensity will be 80% involuntary motor threshold.
Sponsors
Spaulding Rehabilitation Hospital
United States Department of Defense
Brooks Rehabilitation
Congressionally Directed Medical Research Programs
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 18 to 80 years of age * medically stable with medical clearance from study physician to participate * SCI at or below C1 and at or above L2 with at least some sensory or motor function preserved below the neurologic level * non-progressive etiology of spinal injury * American Spinal Injury Association (ASIA) scores of C-D at initial screen * ambulatory (able to complete the 10-meter walk test without support from another person) * chronic injury (define as \> 12 months post-injury) to avoid potential for spontaneous neurological plasticity and recovery
Exclusion criteria
* severe concurrent illness or pain, including unhealed decubiti, severe neuropathic or chronic pain syndrome, severe infection (e.g., urinary tract), hypertension, cardiovascular disease, pulmonary disease, severe osteoporosis, active heterotopic ossification in the lower extremities, severe systemic inflammation * \< 24 on Mini-Mental Exam * severe recurrent autonomic dysreflexia * history of severe cardiovascular/pulmonary complications including hypertension (systolic blood pressure \> 150 mmHg) * pregnancy because of unknown effects of AIH or tSTIM on a fetus (individuals of childbearing potential will not otherwise be excluded) * botulinum toxin injections in lower extremity muscles within the prior three months * history of tendon or nerve transfer surgery in the lower extremity * untreated severe sleep-disordered breathing characterized by uncontrolled hypoxia and sleep fractionation that may impact the outcome of this study. * active implanted devices (e.g., intrathecal baclofen pump) * receiving concurrent electrical stimulation * motor threshold evoked by transcutaneous spinal stimulation \>200 mA
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in walking recovery, assessed by 10 meter walk test (10MWT) | Through study completion, an average of 14 weeks | 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. |
| Rate of change in walking recovery, assessed by 10 meter walk test (10MWT) | Through study completion, an average of 14 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in walking recovery, assessed by 6 minute walk test (6MWT) | Through study completion, an average of 14 weeks | 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. |
| Change in walking recovery, assessed by timed up-and-go (TUG) test | Through study completion, an average of 14 weeks | 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 |
| Change in pain severity, assessed by the Numeric Pain Rating Scale (NPRS) | Through study completion, an average of 14 weeks | 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. |
| Change in cognitive function, assessed by the California Verbal Learning Test (CVLT) | Through treatment completion, an average of 6 weeks | 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. |
| Counts of hypertensive events | Through treatment completion, an average of 6 weeks | 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. |
| Counts of blood pressure measurements | Through treatment completion, an average of 6 weeks | 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. |
| Systemic hypertension incidence rate | Through treatment completion, an average of 6 weeks | 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. |
| Number of autonomic dysreflexia events | Through treatment completion, an average of 6 weeks | 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 |
| Total person-time for autonomic dysreflexia | Through treatment completion, an average of 6 weeks | 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. |
| Autonomic dysreflexia incidence rate | Through treatment completion, an average of 6 weeks | 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. |
| Change in lower extremity strength, assessed by American Spinal Injury Association Impairment Scale (AIS) lower extremity motor scores (LEMS) | Through study completion, an average of 14 weeks | 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. |
| Change in spasticity, assessed by the Spinal Cord Assessment Tool for Spastic Reflexes (SCATS) | Through study completion, an average of 14 weeks | 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. |
| Change in bowel dysfunction, assessed by the Neurogenic Bowel Dysfunction Score (NBDS) v2.1 | Through study completion, an average of 14 weeks | 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. |
| Change in bladder dysfunction, assessed by the Neurogenic Bladder Symptom Score (NBSS) | Through study completion, an average of 14 weeks | 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. |
| Change in walking ability and assistive device use, assessed by Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI). | Through study completion, an average of 14 weeks | 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. |
| Change in physical assistance needed, assessed by Walking Index for Spinal Cord Injury (WISCI) II | Through study completion, an average of 14 weeks | 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. |
| Change in breathing function, assessed by FVC | Through study completion, an average of 14 weeks | Forced vital capacity will be measured, which is the volume of air forcibly expired after a maximal inspiration. |
| Change in apnea hypopnea index | Through treatment completion, an average of 6 weeks | — |
Countries
United States
Contacts
CONTACTNoah Piazza
CONTACTRandy Trumbower, PT, PhD
PRINCIPAL_INVESTIGATORRandy Trumbower, PT, PhD
Harvard Medical School (HMS and HSDM)
Outcome results
None listed