Motor Plasticity, Intermittent Hypoxia and Sleep Apnea

Study Overview
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Brief Summary
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The purpose of this study is to learn about the effect of sleep apnea and low oxygen on muscle strength and lung function in people with chronic spinal cord injury.

Official Title
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Intermittent Hypoxia (IH), Respiratory and Motor Plasticity, and Sleep Apnea in Spinal Cord Injury (SCI)

Conditions
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Sleep Apnea, Obstructive, Spinal Cord Injuries, Hypoxia

Intervention / Treatment
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* Procedure: Induced Acute Intermittent Hypoxia (AIH)
* Device: AIH mask


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 or older, Chronic (≥ 1-year post-injury), non-progressive SCI, Asia Impairment Scale (AIS) C or D, Resting Saturated oxygen (SaO2) ≥ 95%, Cervical injury (C5-C8) Exclusion Criteria: Currently hospitalized, Resting heart rate ≥120 Beats per minute (BPM), Resting systolic blood pressure >180 mmHg, Resting diastolic Blood Pressure >100 mmHg, Self-reported history of unstable angina or myocardial infarction within the previous month, OSA that is being treated with positive airway pressure therapy, Women who know or suspect they may be pregnant or who may become pregnant, Known underlying lung disease, Pregnant Women, Prisoners, Unable to consent

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moderate to Severe Obstructive Sleep Apnea (OSA)<br>Individuals with moderate to severe OSA defined as having an Apnea-hypopnea Index (AHI) that is greater than or equal to 15. | Procedure: Induced Acute Intermittent Hypoxia (AIH)<br>* AIH will be administered on days 1-3. Each day entails 15 and 90 second hypoxic intervals (Fraction of Inspired Oxygen (FIO2) = 0.09) alternating with 60-second normoxic intervals (FIO2 = 0.21).<br>Device: AIH mask<br>* Induced Intermitted hypoxia will be delivered via the AIH mask. The mask has two one-way valves restricting inspiration to the top valve and expiration to the bottom valve. Hypoxic and normoxic gas mixtures will be delivered through the top valve.<br>|
| Active Comparator: Without OSA<br>Individuals without OSA defined as having AHI less than 5. | Procedure: Induced Acute Intermittent Hypoxia (AIH)<br>* AIH will be administered on days 1-3. Each day entails 15 and 90 second hypoxic intervals (Fraction of Inspired Oxygen (FIO2) = 0.09) alternating with 60-second normoxic intervals (FIO2 = 0.21).<br>Device: AIH mask<br>* Induced Intermitted hypoxia will be delivered via the AIH mask. The mask has two one-way valves restricting inspiration to the top valve and expiration to the bottom valve. Hypoxic and normoxic gas mixtures will be delivered through the top valve.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in Motor Function assessed via hand grip strength measured by maximum grip strength (MGS) between participants with moderate to severe OSA and without OSA. | Participants will be instructed to squeeze the hand grip dynamometer with maximal effort for 3-5 seconds. This will be repeated three times for each hand with 1 minute of rest between trials. The highest value obtained will be used as the MGS. | Baseline | 
| The difference in Motor Function assessed via hand grip strength measured by electromyographic (EMG) recordings between participants with moderate to severe OSA and without OSA. | Electrodes will be secured on the participant to measure EMG. Participants will then be asked to press the index finger against a custom lever. The participant will perform three brief maximal voluntary contractions (MVC) for 3-5 seconds separated by 60 seconds of rest. The highest of the three values will be used. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Motor Function assessed via hand grip strength measured by MGS. | Participants will be instructed to squeeze the hand grip dynamometer with maximal effort for 3-5 seconds. This will be repeated three times for each hand with 1 minute of rest between trials. The highest value obtained will be used as the MGS. | Baseline to Day 1 post AIH, Baseline to Day 3 post AIH, Baseline to Day 10, Baseline to Day 17 | 
| Change in Motor Function assessed via hand grip strength measured by EMG recordings. | Electrodes will be secured on the participant to measure EMG. Participants will then be asked to press the index finger against a custom lever. The participant will perform three brief maximal voluntary contractions (MVC) for 3-5 seconds separated by 60 seconds of rest. The highest of the three values will be used. | Baseline to Day 1 post AIH, Baseline to Day 3 post AIH, Baseline to Day 10, Baseline to Day 17 | 
| Change in biomarker levels | Serum Brain-Derived Neurotrophic Factor (BDNF) and Vascular Endothelial Growth Factor (VEGF) biomarker levels in pg/ml will be evaluated. At baseline, the blood samples will be collected after 12 hours of overnight fasting. | Baseline to Day 1 post AIH, Baseline to Day 3 post AIH, Baseline to Day 10, Baseline to Day 17 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuroplasticity, Respiratory Function, Motor Function