Motor Plasticity, Intermittent Hypoxia and Sleep Apnea

• Sponsor: University of Miami (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04017767
• Collaborator: The Craig H. Neilsen Foundation (Other)
• Enrollment: 30
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 35.5
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Sleep Apnea, Obstructive; Spinal Cord Injuries; Hypoxia	Procedure: Induced Acute Intermittent Hypoxia (AIH); Device: AIH mask	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Intermittent Hypoxia (IH), Respiratory and Motor Plasticity, and Sleep Apnea in Spinal Cord Injury (SCI)
• Actual Study Start Date: Jul 16, 2021
• Anticipated Primary Completion Date: Jul 1, 2024
• Anticipated Study Completion Date: Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Moderate to Severe Obstructive Sleep Apnea (OSA) 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); 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).; Device: AIH mask; 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.
Active Comparator: Without OSA Individuals without OSA defined as having AHI less than 5.	Procedure: Induced Acute Intermittent Hypoxia (AIH); 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).; Device: AIH mask; 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.

Outcome Measures

Primary Outcome Measures

1. The difference in Pulmonary Function assessed via Forced Vital Capacity (FVC) between participants with moderate to severe OSA and without OSA. [Baseline]

   Using an open-circuit spirometry, participants will undergo 3 FVC maneuvers. At each maneuver, participant will put on a sterile mouthpiece and nose clips. Participants will begin breathing normally, then they will be instructed to take in a deep breath to maximum inhalation and forcefully exhale. The open-circuit spirometry will store FVC over Force Expiratory Volume after 1 second (FEV1) measurements. The highest of the three trials will be used.

2. The difference in Pulmonary Function assessed via Maximum Inspiratory Pressure (MIP) between participants with moderate to severe OSA and without OSA. [Baseline]

   Participants will be instructed to exhale completely and then pull in hard on a disposable cardboard mouthpiece fitted to a differential pressure gauge. The largest negative pressure sustained for at least one second on the pressure gauge will be noted. In between a minute of rest, the participants will be asked to complete the maneuver two more times. The best of the three recordings will be used for this data outcome.

3. 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. [Baseline]

   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.

4. 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. [Baseline]

   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.

Secondary Outcome Measures

1. Change in Pulmonary Function assessed via FVC [Baseline to Day 1 post AIH, Baseline to Day 3 post AIH, Baseline to Day 10, Baseline to Day 17]

   Using an open-circuit spirometry, participants will undergo 3 FVC maneuvers. At each maneuver, participant will put on a sterile mouthpiece and nose clips. Participants will begin breathing normally, then they will be instructed to take in a deep breath to maximum inhalation and forcefully exhale. The open-circuit spirometry will store FVC over Force Expiratory Volume after 1 second (FEV1) measurements. The highest of the three trials will be used.

2. Change in Pulmonary Function assessed by MIP [Baseline to Day 1 post AIH, Baseline to Day 3 post AIH, Baseline to Day 10, Baseline to Day 17]

   Participants will be instructed to exhale completely and then pull in hard on a disposable cardboard mouthpiece fitted to a differential pressure gauge. The largest negative pressure sustained for at least one second on the pressure gauge will be noted. In between a minute of rest, the participants will be asked to complete the maneuver two more times. The best of the three recordings will be used for this data outcome.

3. Change in Motor Function assessed via hand grip strength measured by MGS. [Baseline to Day 1 post AIH, Baseline to Day 3 post AIH, Baseline to Day 10, Baseline to Day 17]

   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.

4. Change in Motor Function assessed via hand grip strength measured by EMG recordings. [Baseline to Day 1 post AIH, Baseline to Day 3 post AIH, Baseline to Day 10, Baseline to Day 17]

   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.

5. Change in biomarker levels [Baseline to Day 1 post AIH, Baseline to Day 3 post AIH, Baseline to Day 10, Baseline to Day 17]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age 18 or older,

2. Chronic (≥ 1-year post-injury), non-progressive SCI,

3. Asia Impairment Scale (AIS) C or D,

4. Resting Saturated oxygen (SaO2) ≥ 95%,

5. Cervical injury (C5-C8)

Exclusion Criteria:

1. Currently hospitalized,

2. Resting heart rate ≥120 Beats per minute (BPM),

3. Resting systolic blood pressure >180 mmHg,

4. Resting diastolic Blood Pressure >100 mmHg,

5. Self-reported history of unstable angina or myocardial infarction within the previous month,

6. OSA that is being treated with positive airway pressure therapy,

7. Women who know or suspect they may be pregnant or who may become pregnant,

8. Known underlying lung disease,

9. Pregnant Women,

10. Prisoners,

11. Unable to consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami	Miami	Florida	United States	33136

Sponsors and Collaborators

• University of Miami
• The Craig H. Neilsen Foundation

Investigators

• Principal Investigator: Shirin Shafazand, MD, University of Miami

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shirin Shafazand, Professor, University of Miami
• ClinicalTrials.gov Identifier: NCT04017767
• Other Study ID Numbers: 20190415
• First Posted: Jul 12, 2019
• Last Update Posted: Jul 21, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Shirin Shafazand, Professor, University of Miami: Neuroplasticity; Respiratory Function; Motor Function
• Additional relevant MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Spinal Cord Injuries; Hypoxia

Study Results

No Results Posted as of Jul 21, 2021