Treatment of Sleep Apnea in Patients With Cervical Spinal Cord Injury

Spinal Cord Injury Clinical Trial

Official title:

Treatment of Sleep Apnea in Patients With Cervical Spinal Cord Injury

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02922894
• Other study ID #: 1607015110
• Status: Recruiting
• Phase: Phase 4
• Start date: June 9, 2017
• Est. completion date: June 30, 2024

Study information

• Verified date: November 2023
• Source: John D. Dingell VA Medical Center
• Contact: M Safwan Badr, M.D.
• Phone: 313-576-3548
• Email: m.badr[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will investigate potential therapeutic approaches for sleep-disordered breathing (SDB) in patients with chronic cervical spine injury (>6 months post-injury).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 30, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

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).

Related Conditions & MeSH terms

• Apnea
• Sleep Apnea
• Sleep Apnea Syndromes
• Spinal Cord Injuries
• Spinal Cord Injury
• Wounds and Injuries

Intervention

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.
• Supplemental oxygen
Supplemental oxygen therapy for 6 weeks

Drug:
• Trazodone
100mg before bedtime
• Placebo
One placebo pill before-bedtime

Procedure:
• Sham
Room air will be administered instead of episodic hypoxia or supplemental oxygen..

Locations

Country	Name	City	State
United States	John D. Dingell VA Medical Center	Detroit	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
John D. Dingell VA Medical Center	United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Tidal Volume	Change in tidal volume from baseline to recovery period.	1 Week
Primary	Change in CO2 reserve (Delta-PETCO2-AT)	CO2 reserve is the requisite change to induce central apnea is referred to as the CO2 reserve, which can be positive or negative	1 Week
Primary	Change in Apnea Hypopnea Index (AHI)	AHI is used to indicate the severity of sleep apnea.	1 week
Primary	Change in hypocapnic apneic threshold	The nadir pressure in the upper airway (supra-glotic pressure) prior to the occurrence of an arousal. This is a physiological parameter.	1 week