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Treatment of Sleep Apnea in Patients With Cervical Spinal Cord Injury

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ClinicalTrials.gov Identifier: NCT02922894
Recruitment Status : Recruiting
First Posted : October 4, 2016
Last Update Posted : May 30, 2019
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
John D. Dingell VA Medical Center

Tracking Information
First Submitted Date  ICMJE September 23, 2016
First Posted Date  ICMJE October 4, 2016
Last Update Posted Date May 30, 2019
Actual Study Start Date  ICMJE June 9, 2017
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2019)
  • Change in Tidal Volume [ Time Frame: 1 Week ]
    Change in tidal volume from baseline to recovery period.
  • Change in CO2 reserve (Delta-PETCO2-AT) [ Time Frame: 1 Week ]
    CO2 reserve (Delta-PETCO2-AT) will be measured after the one week treatment with trazodone and placebo and will be compared to baseline.
  • Change in Apnea Hypopnea Index (AHI) [ Time Frame: 1 week ]
    AHI will be measured after the one week treatment with trazodone and placebo and compared to baseline.
  • Change in hypocapnic apneic threshold [ Time Frame: 1 week ]
    Hypocapnic apneic threshold with will be measured after the one week treatment with trazodone and placebo and compared to baseline.
Original Primary Outcome Measures  ICMJE
 (submitted: October 3, 2016)
  • Change in Tidal Volume [ Time Frame: 1 Week ]
    Change in tidal volume from baseline to recovery period.
  • Change in CO2 reserve (Delta-PETCO2-AT) [ Time Frame: 1 Week ]
    CO2 reserve (Delta-PETCO2-AT) will be measured after the one week treatment with trazodone and placebo and will be compared to baseline.
  • Change in Apnea Hypopnea Index (AHI) [ Time Frame: 1 week ]
    AHI will be measured after the one week treatment with trazodone and placebo and compared to baseline.
  • Change in Expiratory Reserve Volume [ Time Frame: 1 week ]
    Change in expiratory reserve volume from baseline to recovery period.
  • Change in hypocapnic apneic threshold [ Time Frame: 1 week ]
    Hypocapnic apneic threshold with will be measured after the one week treatment with trazodone and placebo and compared to baseline.
Change History Complete list of historical versions of study NCT02922894 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treatment of Sleep Apnea in Patients With Cervical Spinal Cord Injury
Official Title  ICMJE Treatment of Sleep Apnea in Patients With Cervical Spinal Cord Injury
Brief Summary This study will investigate potential therapeutic approaches for sleep-disordered breathing (SDB) in patients with chronic cervical spine injury (>6 months post-injury).
Detailed Description

Patients with cervical spinal cord injury demonstrate central sleep disordered breathing manifesting as central sleep apnea or a periodic breathing pattern. Understanding the causes of central sleep apnea may be critically important to understanding upper airway obstruction in susceptible individuals, given the critical role of ventilatory motor output in maintaining upper airway patency as evidenced by upper airway narrowing or occlusion at the nadir of ventilator drive during periodic breathing. This study is likely to identify therapeutic strategies that could be tested in large clinical trials, with the ultimate goal of improving quality of life among patients with cervical SCI who also experience central sleep disordered breathing.

To this end the research proposal is aimed as follows:

Specific Aim 1: Test the hypothesis that patients with cervical SCI will demonstrate greater magnitude of long-term facilitation (LTF) following episodic hypoxia during sleep, compared to patients with thoracic Spinal cord injury. This aim will be accomplished by measuring the effect of acute episodic hypoxic ventilation and upper airway mechanics in both groups.

Specific Aim 2: Test the hypothesis that dampening peripheral chemoreceptor activity in patients with cervical SCI and central sleep disordered breathing (SDB) with supplemental oxygen will reduce central respiratory events and decrease respiratory variability during sleep. The aim will be accomplished by providing supplemental oxygen to participants with cervical SCI and central SDB.

Specific Aim 3: Test the hypothesis that administration of trazodone, in patients with cervical spinal cord injury and central SDB will decrease respiratory related arousals and central apnea index, and the propensity to develop central apnea, compared to placebo. To accomplish this aim, the investigators will test the acute effect of trazodone on respiratory related arousals and central sleep apnea, and the chronic effect on central apnea indices and the CO2 reserve.

The investigators will study subjects with SCI at T6 or above who are not on artificial ventilation. To characterize the sleep and breathing state of each subject, polysomnography and upper airway collapsibility will be measured at baseline. Then the following experiments will be conducted: an episodic hypoxia protocol vs normoxia will be used to determine whether cervical SCI will demonstrate greater magnitude of LTF. Experiments will be conducted to see whether dampening peripheral chemoreceptor activity in cervical SCI by giving supplemental oxygen will reduce the central respiratory events and reduce the breathing variability during sleep. A cross over experiment will be done to see whether administration of trazodone in patients with cervical SCI and central SDB decreases respiratory-related arousals and central apnea. The participant will be given the drug/placebo for one week then cross over after a 1 week wash out period to placebo.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Other
Condition  ICMJE
  • Sleep Apnea
  • Spinal Cord Injury
Intervention  ICMJE
  • Procedure: Acute episodic hypoxia
    The subjects will undergo 30 minutes of baseline monitoring followed by 15 episodes of one minute of episodic hypoxia with supplemental CO2 to maintain isocapnia. This is followed by a 45 minute recovery period.
  • Procedure: Supplemental oxygen
    Supplemental oxygen therapy for 6 weeks
  • Drug: Trazodone
    100mg before bedtime
  • Drug: Placebo
    One placebo pill before-bedtime
  • Procedure: Sham
    Room air will be administered instead of episodic hypoxia or supplemental oxygen..
Study Arms  ICMJE
  • Experimental: Acute episodic hypoxia
    To test development of ventilatory augmentation following episodic hypoxia, defined as increased Hypoxic Ventilatory Response (HVR) from early to late hypoxic exposure episodes.
    Interventions:
    • Procedure: Acute episodic hypoxia
    • Procedure: Sham
  • Experimental: Supplemental oxygen
    To use supplemental oxygen to decrease peripheral chemoreceptor activity in patients with SCI and central SDB. In addition, perform a repeat evaluation after treatment with supplemental oxygen or sham O2 for 6 weeks to determine if correction of chronic intermittent hypoxia, which mitigates sensory LTF, results in decreased propensity to central apnea.
    Interventions:
    • Procedure: Supplemental oxygen
    • Procedure: Sham
  • Experimental: Trazodone or placebo
    examine the effect of trazodone on breathing during sleep
    Interventions:
    • Drug: Trazodone
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 3, 2016)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2021
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. healthy adults between the ages of 18 - 89
  2. chronic spinal cord injury patients (T6 and above), > 3 months since injury and not on mechanical ventilation, and have not received mechanical ventilation via tracheostomy in the past.

Exclusion Criteria:

  1. subjects ≤ 17 yrs old
  2. Pregnant and lactating females
  3. History of head trauma that resulted in neurological symptoms or loss of consciousness
  4. advanced heart, lung, metabolic, liver or chronic kidney disease.
  5. severe obstructive or restrictive respiratory defect by PFTs or history of tracheostomy
  6. extreme obesity defined for this protocol as BMI ≥ 40 kg/m2 (to avoid the effect of morbid obesity on ventilation.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 89 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: M Safwan Badr, M.D. 313-576-3548 m.badr@va.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02922894
Other Study ID Numbers  ICMJE 1607015110
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party John D. Dingell VA Medical Center
Study Sponsor  ICMJE John D. Dingell VA Medical Center
Collaborators  ICMJE United States Department of Defense
Investigators  ICMJE
Principal Investigator: M Safwan Badr, M.D. John D. Dingell VA Medical Center
PRS Account John D. Dingell VA Medical Center
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP