NCT05589753

Sleep Disordered Breathing With Opioid Use

Targeting Chemoreceptor Control of Breathing During Sleep to Mitigate Opioid-Associated Sleep Disordered Breathing

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Sponsor: VA Office of Research and Development · Federal
• Sex: All
• Age: 18 Years – 89 Years
• Healthy volunteers: Accepted

Summary

There is an increased risk for sleep disordered breathing (SDB), sleep-related hypoventilation and irregular breathing in individuals on chronic prescription opioid medications. Almost 30% of a veteran sleep clinic population had opioid-associated central sleep apnea (CSA). The proposal aims to identity whether oxygen and acetazolamide can be effective in reducing unstable breathing and eliminating sleep apnea in chronic opioid use via different mechanisms. We will study additional clinical parameters like quality of life, sleep and pain in patients with and without opioid use. This proposal will enhance the investigators' understanding of the pathways that contribute to the development of sleep apnea with opioid use. The investigators expect that the results obtained from this study will positively impact the health of Veterans by identifying new treatment modalities for sleep apnea.

Detailed description

In a national sample of Veterans, SDB was a significant risk factor for opioid-related toxicity and overdose; and the presence of CSA combined with chronic prescription opioid use compounded the mortality risk. There are only limited and partially effective therapies for this sleep disorder and the exact mechanisms by which opioids produce SDB in adults remain unclear, and varied and conflicting ventilatory control mechanisms have been suggested. This proposal will investigate whether alternative therapies can be developed by modulating specific physiologic mechanisms of ventilatory control. Specifically, the investigators will study effects of chronic oral prescription opioids on chemoresponsiveness and cerebrovascular responsiveness (CVR) (Aim 1); and whether interventions with sustained hyperoxia (Aim 2) and acetazolamide (Aim 3) will reduce the apneic threshold (AT) to alleviate breathing instability and SDB in chronic prescription opioid-associated SDB. The proposed aims will also allow us to delineate key mechanisms of breathing instability with opioid and without opioid use. The information garnered from the proposed experiments will drive development of novel personalized therapies to reduce SDB associated with chronic opioids in Veterans and, ultimately, will positively impact their long-term health and well-being.

Conditions

• Sleep Apnea
• Opioid Use
• Sleep Disordered Breathing

Interventions

Type	Name	Description
OTHER	Hyperoxia	The ventilatory effects of brief hyperoxia will be assessed by analyzing control breaths on room air immediately preceding the hyperoxic exposure, and comparing with the primary end-point, nadir minute ventilation breath, immediately following the brief hyperoxic exposure.
DRUG	Acetazolamide	Participants with sleep apnea will ingest capsules containing either placebo or acetazolamide 500 mg twice a day for 6 days. On the final 4 consecutive nights while still on ACZ, the investigators will perform i) physiology tests and ii) in-lab follow-up PSG.

Timeline

• Start date: 2019-05-02
• Primary completion: 2026-12-31
• Completion: 2027-03-31
• First posted: 2022-10-21
• Last updated: 2025-07-18

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study