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Motor Plasticity, Intermittent Hypoxia and Sleep Apnea

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ClinicalTrials.gov Identifier: NCT04017767
Recruitment Status : Not yet recruiting
First Posted : July 12, 2019
Last Update Posted : July 12, 2019
Sponsor:
Collaborator:
The Craig H. Neilsen Foundation
Information provided by (Responsible Party):
Shirin Shafazand, University of Miami

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 Not Applicable

Detailed Description:

The overall goal of this pilot project is to determine the effect of obstructive sleep apnea (OSA) and its associated chronic intermittent hypoxia (CIH) on neuroplasticity, and respiratory, and motor functions in subjects with chronic spinal cord injury (SCI), exposed to acute intermittent hypoxia (AIH). We will further explore changes in the biomarkers of AIH in the setting of OSA and SCI.

Specific Aim 1: Determine whether there is a baseline difference in pulmonary and motor function in subjects with chronic SCI with and without OSA.

Hypothesis 1: We hypothesize that subjects with moderate to severe OSA and chronic SCI will have worse pulmonary function (measured by forced vital capacity [FVC], and maximum inspiratory pressure [MIP]), and hand grip strength (measured by force and EMG activation of hand muscles) compared with SCI subjects without OSA.

Specific Aim 2: Determine whether moderate to severe OSA, attenuates the respiratory and motor response to AIH in chronic SCI.

Hypothesis 2: We hypothesize that subjects with moderate to severe OSA and chronic SCI will have no change in baseline pulmonary function, and hand grip strength, when exposed to a 3-day AIH protocol. By contrast, SCI subjects without OSA will show an improvement in all measured outcomes.

Specific Aim 3: Determine whether there is a difference in levels of AIH biomarkers including BDNF and VEGF in subjects with chronic SCI with and without OSA.

Hypothesis 3: We hypothesize that compared with subjects without OSA, those with moderate to severe OSA and chronic SCI will have lower BDNF, and higher VEGF at baseline with no change in these biomarker levels when exposed to a 3-day AIH protocol. By contrast, SCI subjects without OSA will show an increase in baseline VEGF and BDNF levels when exposed to the AIH protocol.


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Study Type : Interventional  (Clinical Trial)
Estimated 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)
Estimated Study Start Date : October 1, 2019
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : December 1, 2022

Resource links provided by the National Library of Medicine


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.




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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04017767


Contacts
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Contact: Shirin Shafazand, MD 305-243-7888 sshafazand@med.miami.edu

Locations
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United States, Florida
University of Miami Not yet recruiting
Miami, Florida, United States, 33136
Contact: Shirin Shafazand    305-243-7888    sshafazand@med.miami.edu   
Principal Investigator: Shirin Shafazand, MD         
Sub-Investigator: Mark Nash, PhD         
Sub-Investigator: Katie Gant, PhD         
Sponsors and Collaborators
University of Miami
The Craig H. Neilsen Foundation
Investigators
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Principal Investigator: Shirin Shafazand, MD University of Miami

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Responsible Party: Shirin Shafazand, Professor, University of Miami
ClinicalTrials.gov Identifier: NCT04017767     History of Changes
Other Study ID Numbers: 20190415
First Posted: July 12, 2019    Key Record Dates
Last Update Posted: July 12, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Shirin Shafazand, University of Miami:
Neuroplasticity
Respiratory Function
Motor Function
Additional relevant MeSH terms:
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Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Spinal Cord Injuries
Hypoxia
Wounds and Injuries
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Trauma, Nervous System