Sleep Disordered Breathing With Opioid Use

NCT05589753 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: PULM-003-18F1904002203
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sleep Apnea; Opioid Use; Sleep Disordered Breathing

Outcome Measures

Primary Outcomes (4)

• Apneic threshold- a measure of breathing instability

  Measures of breathing instability including: Apneic threshold: this is the end-tidal Co2 at which a central apnea closes to a hypopnea is produced.

  2 days to 30 days

• Cerebrovascular responsiveness to carbon-dioxide

  Cerebrovascular response to different levels of CO2: this is a measure of the response of the cerebral blood flow to changes in carbon dioxide levels and is used as a measure of ventilatory control of breathing

  7 days

• Ventilatory responsiveness

  Hypocapnic ventilatory response; this is calculated as the change in minute ventilation for corresponding changes in PETCO2.

  2 days to 30 days

• Carbon -dioxide reserve

  This is a derived measure. This is calculated as the difference between the apneic threshold PETCO2 (given above) and the control PETCO2.

  2 days to 30 days

Secondary Outcomes (1)

• Apnea hypopnea index

  2 days to 30 days

Study Arms (2)

Hyperoxia

EXPERIMENTAL

Determine the effect of sustained hyperoxia overnight vs room air overnight on ventilatory control during sleep, including the apneic threshold, carbon-dioxide reserve and chemosensitivity measured via pressure support ventilation (PSV) during non-rapid eye movement sleep (NREM) sleep.

Other: Hyperoxia

Acetazolamide (ACZ)

EXPERIMENTAL

Determine the effect of acetazolamide on cerebrovascular responsiveness to CO2 during wake and sleep. Participants will receive oral ACZ therapy for 6 days, While on the medication following studies will be performed - experimental night study, experimental day study, polysomnography night study (PSG).

Drug: Acetazolamide

Interventions

Hyperoxia OTHER

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.

Also known as: oxygen

Hyperoxia

Acetazolamide DRUG

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.

Also known as: ACZ

Acetazolamide (ACZ)

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Veterans, age 18-89 years
• Veterans with prescription opioids

You may not qualify if:

• Patients with BMI\>40kg/m2 will be excluded to avoid the effects of morbid obesity on pulmonary mechanics and ventilatory control
• Patients with history of unresolved/untreated cardiac disease, including recent myocardial infarction, recent bypass surgery, untreated atrial and ventricular tachy-bradycardias
• Congestive heart failure with Cheyne-Stokes respiration (CSR)
• Current unstable angina
• Recent stroke
• Untreated schizophrenia
• Untreated hypothyroidism
• Unresolved seizure disorder
• Severe respiratory, neurological, liver and renal diseases
• Unstable psychiatric disorders/untreated PTSD
• Traumatic brain injury
• Pregnant women
• Significant sleep disorder such as narcolepsy, parasomnias disorder
• Failure to give informed consent
• Patients on tramadol and suboxone/buprenorphine

Sponsors & Collaborators

• VA Office of Research and Development: lead
• John D. Dingell VA Medical Center: collaborator

Study Sites (1)

John D. Dingell VA Medical Center, Detroit, MI

Detroit, Michigan, 48201-1916, United States

RECRUITING

MeSH Terms

Conditions

Sleep Apnea Syndromes

Interventions

Oxygen; Acetazolamide

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Chalcogens; Elements; Inorganic Chemicals; Gases; Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Susmita Chowdhuri, MD MS

  John D. Dingell VA Medical Center, Detroit, MI

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruchi Rastogi, MS

CONTACT

(313) 576-4464; ruchi.rastogi@va.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2022
• First Posted: October 21, 2022
• Study Start: May 2, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)