Treatments for Sleep Apnea in Spinal Cord Injury

Overseen By M Safwan Badr, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: John D. Dingell VA Medical Center

Disqualifiers: Pregnancy, Head trauma, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment for sleep apnea in spinal cord injury patients?

The research indicates that sleep apnea is more common in older patients with spinal cord injury, and factors like reduced ventilatory function and sleep posture may contribute to this. Additionally, individuals with cervical spinal cord injury show a higher short-term ventilatory response to acute intermittent hypoxia, which could suggest potential benefits of treatments targeting hypoxia in managing sleep apnea in this population. ^{1 2 3 4 5}

Is intermittent hypoxia safe for humans with spinal cord injury?

Intermittent hypoxia has been studied in both animals and humans, showing potential for improving breathing function after spinal cord injury. While the studies focus on its effectiveness, they do not report significant safety concerns, suggesting it is generally safe for use in humans. ^{1 2 4 6 7}

How does the treatment of acute episodic hypoxia differ for sleep apnea in spinal cord injury?

Acute episodic hypoxia is unique because it involves brief, repeated exposure to low oxygen levels, which can promote neuroplasticity (the brain's ability to reorganize itself) and improve breathing function in spinal cord injury patients. This approach is different from standard treatments as it aims to enhance the body's natural ability to recover respiratory function rather than just managing symptoms. ^{1 2 3 5 7}

Research Team

M Safwan Badr, M.D.

Principal Investigator

John D. Dingell VA Medical Center

Eligibility Criteria

This trial is for adults aged 18-89 with chronic cervical spinal cord injury (T6 and above), at least 3 months post-injury, who are not on mechanical ventilation. It excludes those with extreme obesity (BMI ≥ 40 kg/m2), under 17 years old, pregnant or lactating women, severe respiratory defects, history of significant head trauma, or advanced organ diseases.

Inclusion Criteria

I have a spinal cord injury above T6, it's been over 3 months, and I've never needed a ventilator.

I am between 18 and 89 years old and healthy.

Exclusion Criteria

I have severe breathing problems or have had a tracheostomy.

You have a very high body mass index (BMI) of 40 or more, which could affect your breathing.

I am 17 years old or younger.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Polysomnography and upper airway collapsibility are measured to characterize the sleep and breathing state of each subject

1 week

Treatment

Participants undergo various experimental treatments including episodic hypoxia, supplemental oxygen, and trazodone administration

6 weeks

Crossover

Participants switch from trazodone to placebo or vice versa after a 1-week washout period

2 weeks

Follow-up

Participants are monitored for changes in CO2 reserve, tidal volume, hypocapnic apneic threshold, and Apnea Hypopnea Index

1 week

Treatment Details

Interventions

• Acute episodic hypoxia
• Placebo
• Sham
• Supplemental oxygen
• Trazodone

Trial Overview The study explores treatments for sleep-disordered breathing in patients with cervical spine injuries. Interventions include supplemental oxygen, acute episodic hypoxia treatment, the drug Trazodone versus placebo controls like sham procedures to assess their effectiveness.

Participant Groups

Group I: Trazodone or placebo Experimental Treatment 2 Interventions

examine the effect of trazodone on breathing during sleep

Group II: Supplemental oxygen Experimental Treatment 2 Interventions

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 III: Acute episodic hypoxia Experimental Treatment 2 Interventions

To test development of ventilatory augmentation following episodic hypoxia, defined as increased Hypoxic Ventilatory Response (HVR) from early to late hypoxic exposure episodes.

Who Is Running the Clinical Trial?

John D. Dingell VA Medical Center

Lead Sponsor

Trials

10

Recruited

1,100+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

Individuals with cervical spinal cord injury (SCI) showed a significantly higher short-term hypoxic ventilatory response (HVR) during acute intermittent hypoxia (AIH) compared to those with thoracic SCI, indicating a potentially different respiratory response mechanism in cervical SCI patients.

Despite the increased short-term HVR, there was no evidence of long-term ventilatory facilitation following AIH in either cervical or thoracic SCI groups, suggesting that while acute responses may differ, long-term adaptations in ventilation are not observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetraplegia is associated with increased hypoxic ventilatory response during nonrapid eye movement sleep. Vaughan, S., Sankari, A., Carroll, S., et al.[2023]

Acute intermittent hypoxia has shown promise as a therapeutic strategy to improve respiratory function in individuals with cervical spinal cord injuries, based on studies that demonstrate its potential to induce neuroplasticity and functional recovery.

Research in animal models has laid the groundwork for exploring the effects of acute intermittent hypoxia in human clinical studies, highlighting its potential to restore breathing function after spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent hypoxia and respiratory recovery in pre-clinical rodent models of incomplete cervical spinal cord injury. Gonzalez-Rothi, EJ., Lee, KZ.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Prevalence of sleep apnoea in patients over 40 years of age with spinal cord lesions. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Factors associated with sleep apnea in men with spinal cord injury: a population-based case-control study. [2011]

3. United States pubmed.ncbi.nlm.nih.gov

Estimated prevalence of obstructive sleep apnea-hypopnea syndrome after cervical cord injury. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Tetraplegia is associated with increased hypoxic ventilatory response during nonrapid eye movement sleep. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Obstructive sleep apneas in relation to severity of cervical spinal cord injury. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Intermittent Hypoxia Induces Greater Functional Breathing Motor Recovery as a Fixed Rather Than Varied Duration Treatment after Cervical Spinal Cord Injury in Rats. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Intermittent hypoxia and respiratory recovery in pre-clinical rodent models of incomplete cervical spinal cord injury. [2021]