Pairing Intermittent Hypoxia and Transcutaneous Electrical Spinal Cord Stimulation to Promote Arm Use After Cervical SCI

Study Overview
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Brief Summary
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The purpose of this study is to test the efficacy of mild breathing bouts of low oxygen (intermittent hypoxia) combined with transcutaneous electrical spinal cord stimulation on restoring hand function in persons with chronic incomplete spinal cord injury.

Detailed Description
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The goal of this study is to determine the effectiveness of repeatedly breathing mild bouts of low oxygen for brief periods (termed acute intermittent hypoxia (AIH)) combined with non-invasive transcutaneous electrical spinal cord stimulation (TESS) on restoring hand function in persons with chronic incomplete SCI. The fundamental hypothesis guiding this proposal is that daily AIH+TESS engage excitatory and inhibitory pathways, which converge on a common plasticity-promoting cascade that induces greater recovery of hand function than either one alone. Both treatments appear to enhance motor function in persons with cervical SCI. Despite their independent effects on promoting functional benefits, it is not yet know if they may promote greater functional benefits when combined. To be effective as a long-term rehabilitation strategy, it is essential to determine the efficacy of combined protocols of recurring AIH+TESS.

Official Title
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Combinatorial Treatment of Acute Intermittent Hypoxia and Transcutaneous Electrical Spinal Cord Stimulation to Improve Hand Function in People With Cervical Spinal Cord Injury

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Other: AIH - Intermittent Hypoxia - hypoxia air mixture
* Other: SHAM - Intermittent Room Air - room air mixture
* Device: TESS - Transcutaneous Electrical Spinal Cord Stimulation + Functional Task Practice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 65 years old medically stable with medical clearance from physician to participate SCI at or below C3 and at or above C7 non-progressive etiology of spinal injury American Spinal Injury Association Impairment Scale (AIS) C-D at initial screen at least 1 year post-injury (chronic) difficulty independently performing hand functions in activities of daily living Exclusion Criteria: dependence on ventilation support implanted stimulator (e.g. diaphragm pacing by phrenic nerve stimulation, vagus nerve stimulator, pacemaker, cochlear implant, epidural stimulator, baclofen pump, etc.) spinal cord injury related complications including unhealed pressure sore, severe neuropathic or chronic pain syndrome, history of frequent autonomic dysreflexia, infection (e.g. urinary tract), cardiovascular disease (e.g. deep vein thrombosis), pulmonary disease, heterotopic ossification in the upper extremities, severe osteoporosis, unhealed fracture, contracture of the upper extremity joints received botulinum toxin injections in upper extremity muscles in the prior 6 months history of tendon or nerve transfer surgery in the upper extremity history of additional neurologic disease, such as stroke, multiple sclerosis, traumatic brain injury, peripheral neuropathy (diabetic polyneuropathy, entrapment neuropathy, etc.) or peripheral nerve injury in the upper extremity history of concomitant diseases that would prevent full participation in intensive exercise therapy, such as uncontrolled hypertension, rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.), pulmonary disease, active cancer, chronic contagious disease, etc. anticoagulation medication pregnancy history of allergic reaction or any skin reaction to use of adhesive electrodes

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intermittent Hypoxia (AIH) + Transcutaneous Electrical Spinal Cord Stimulation (TESS)<br>Intervention: AIH - Intermittent Hypoxia - hypoxia air mixture Dosage: 10% oxygen Frequency: 1.5 minutes bouts of low oxygen with 1.0 minute intervals of room air Duration: 38 minutes TESS + Functional Task Practice Duration: 45 minutes | Other: AIH - Intermittent Hypoxia - hypoxia air mixture<br>* Participants will breathe intermittent low oxygen via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of fraction of inspired oxygen (FIO2)=0.10±0.02 (hypoxia). Participants will receive treatment 4 times per week.<br>Device: TESS - Transcutaneous Electrical Spinal Cord Stimulation + Functional Task Practice<br>* Participants will receive transcutaneous electrical stimulation to the cervical spinal cord using the TESCoN device developed by SpineX, Inc. Training will consist of progressive functional task practice for upper extremity motor training. A total of 24 treatment sessions, which will last 45 minutes per session, will be completed in 3 weeks (4 days/week) per crossover arm.<br>|
| Sham Comparator: Intermittent Room Air (SHAM) + Transcutaneous Electrical Spinal Cord Stimulation (TESS)<br>Intervention: SHAM - Intermittent Room Air - room air mixture Dosage: 21% oxygen Frequency: 1.5 minutes bouts of room air with 1.0 minute intervals also of room air Duration: 38 minutes TESS + Functional Task Practice Duration: 45 minutes | Other: SHAM - Intermittent Room Air - room air mixture<br>* Participants will breathe intermittent room air via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of fraction of inspired oxygen (FIO2)=0.21±0.02 (normoxia). Participants will receive treatment 4 times per week.<br>Device: TESS - Transcutaneous Electrical Spinal Cord Stimulation + Functional Task Practice<br>* Participants will receive transcutaneous electrical stimulation to the cervical spinal cord using the TESCoN device developed by SpineX, Inc. Training will consist of progressive functional task practice for upper extremity motor training. A total of 24 treatment sessions, which will last 45 minutes per session, will be completed in 3 weeks (4 days/week) per crossover arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in upper extremity function | Change in upper extremity function performance metrics after treatment assessed using the Graded Redefined Assessment of Strength, Sensation and Prehension test (GRASSP). | Baseline, once each intervention week (days 5, 10, and 15), and once at followup (week 8) | 
| Change in upper extremity strength | Change in upper extremity strength after treatment assessed using dynamometers to measure pinch and grip forces. | Baseline, once each intervention week (days 5, 10, and 15), and once at followup (week 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Superiority of combined AIH + TESS Therapy vs. TESS alone to improve upper extremity function | Superiority as demonstrated by statistically significant difference in the improvement of subjects' upper extremity function between the AIH and SHAM treatment arms assessed using the Graded Redefined Assessment of Strength, Sensation and Prehension test (GRASSP). | Baseline, once each intervention week (days 5, 10, and 15), and once at followup (week 8) | 
| Superiority of combined AIH + TESS Therapy vs. TESS alone to improve upper extremity strength | Superiority as demonstrated by statistically significant difference in the improvement of subjects' upper extremity strength between the AIH and SHAM treatment arms assessed using dynamometers to measure pinch and grip forces. | Baseline, once each intervention week (days 5, 10, and 15), and once at followup (week 8) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypoxia, spinal cord injury, rehabilitation, function, low oxygen