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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for sleep apnea in individuals with chronic spinal cord injuries. Researchers are testing three approaches: supplemental oxygen, acute episodic hypoxia (short periods of low oxygen), and trazodone (a medication often used for sleep disorders). The goal is to determine which method best improves breathing during sleep. Individuals with a cervical spine injury for more than 6 months who struggle with sleep-disordered breathing might be suitable for the study. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, allowing researchers to understand how they benefit more patients.

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 is the safety track record for these treatments?

Research has shown that the treatments tested for sleep apnea in individuals with spinal cord injuries have varying safety levels.

For acute episodic hypoxia, studies indicate it is generally safe. This treatment helps the body adapt to reduced oxygen levels for short periods, potentially improving breathing. Importantly, research suggests it does not harm brain function or cerebral blood flow.

For supplemental oxygen, safety data is less detailed in this specific context. However, its widespread use in medical settings suggests it is generally safe.

Regarding trazodone, a medication sometimes used for sleep issues, evidence suggests it may not be very effective for breathing problems in spinal cord injury patients. However, studies have monitored side effects, indicating careful safety oversight.

Overall, these treatments are being tested in a Phase 4 trial, which typically confirms safety in larger groups after earlier studies have established safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for sleep apnea in individuals with spinal cord injury because they explore novel mechanisms of action. Unlike traditional treatments like CPAP machines, which primarily focus on physically maintaining open airways, the acute episodic hypoxia treatment aims to enhance the body's natural ventilatory response through controlled hypoxic episodes. This could potentially reduce the occurrence of central sleep apnea by training the body to better respond to low oxygen levels. Additionally, the use of supplemental oxygen targets the peripheral chemoreceptors, which may help decrease central apnea by addressing chronic intermittent hypoxia. These innovative approaches offer new ways to potentially improve sleep quality and breathing stability in affected individuals.

What evidence suggests that this trial's treatments could be effective for sleep apnea in spinal cord injury?

Research has shown that short periods of breathing low-oxygen air, tested in this trial as acute episodic hypoxia, can improve breathing in people with spinal cord injuries. This method might enhance the body's natural breathing response, leading to better breathing over time. Another treatment arm in this trial involves supplemental oxygen, which evidence suggests can improve sleep quality by reducing nighttime breathing problems, potentially decreasing episodes of sleep apnea. However, studies found that trazodone, also tested in this trial, does not effectively improve breathing issues during sleep for people with spinal cord injuries. ^{2 3 4 6 7}

Who Is on the Research Team?

M Safwan Badr, M.D.

Principal Investigator

John D. Dingell VA Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7491397/

Mild to Moderate Sleep Apnea Is Linked to Hypoxia-induced ...

Many individuals with SCI exhibit mild to moderate SDB (6), leading to extended periods of nocturnal high-dose intermittent hypoxia. Because chronic ...

2.

brooksrehab.org

brooksrehab.org/resources/breathing-less-oxygen-may-help-sci-survivors-breathe-better/

Breathing Less Oxygen May Help SCI Survivors ...

Researchers believe that combining respiratory therapy with bouts of breathing air with less oxygen might be a solution to help them breathe better.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6688981/

Sleep-Disordered Breathing and Spinal Cord Injury

Recent data in individuals with acute cervical SCI reported that increased SDB severity was associated with worse attention, information processing, and short- ...

4.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1569904824001514

Safety and effectiveness of acute intermittent hypoxia ...

Acute intermittent hypoxia enhances strength, and modulates spatial distribution of muscle activation in persons with chronic incomplete spinal cord injury ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03644277

A Multi-Center Clinical Trial in Individuals With Spinal Cord ...

The overall objective of this project is to investigate the effectiveness of daily acute intermittent hypoxia therapy (dAIH), coupled with massed practice ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12321890/

Mild intermittent hypoxia may improve autonomic ...

Systolic autonomic dysreflexia improved by 46% ± 14% and orthostatic hypotension improved by 160% ± 63% after MIH. Reductions in the apnea ...

7.

clinicaltrials.gov

clinicaltrials.gov/ct2/show/NCT03736382

Mild Intermittent Hypoxia and Its Multipronged Effect on ...

Secondary outcomes include blood pressure measured during sleep over 24 hours, along with the measurement of beat to beat blood pressure, autonomic nervous ...