Treatment of Sleep Apnea in Patients With Cervical Spinal Cord Injury

NCT ID: NCT02922894

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-09
• Study Completion Date: 2026-06-30

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.

Conditions

Sleep Apnea; Spinal Cord Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Acute episodic hypoxia

Intervention Type: PROCEDURE

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.

Sham

Intervention Type: PROCEDURE

Room air will be administered instead of episodic hypoxia or supplemental oxygen..

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.

Group Type: EXPERIMENTAL

Supplemental oxygen

Intervention Type: PROCEDURE

Supplemental oxygen therapy for 6 weeks

Sham

Intervention Type: PROCEDURE

Room air will be administered instead of episodic hypoxia or supplemental oxygen..

Trazodone or placebo

examine the effect of trazodone on breathing during sleep

Group Type: EXPERIMENTAL

Trazodone

Intervention Type: DRUG

100mg before bedtime

Placebo

Intervention Type: DRUG

One placebo pill before-bedtime

Interventions

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.

Intervention Type: PROCEDURE

Supplemental oxygen

Supplemental oxygen therapy for 6 weeks

Intervention Type: PROCEDURE

Trazodone

100mg before bedtime

Intervention Type: DRUG

Placebo

One placebo pill before-bedtime

Intervention Type: DRUG

Sham

Room air will be administered instead of episodic hypoxia or supplemental oxygen..

Intervention Type: PROCEDURE

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

John D. Dingell VA Medical Center

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

M Safwan Badr, M.D.

Role: PRINCIPAL_INVESTIGATOR

John D. Dingell VA Medical Center

Locations

John D. Dingell VA Medical Center

Detroit, Michigan, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

M Safwan Badr, M.D.

Role: CONTACT

m.badr@va.gov

313-576-3548

Facility Contacts

M. Safwan Badr, MD

Role: primary

313-576-3548

Other Identifiers

CDMRP-SC150201

Identifier Type: OTHER

Identifier Source: secondary_id

1607015110

Identifier Type: -

Identifier Source: org_study_id