Supplemental Oxygen for Sleep-Disordered Breathing in Adults With Chronic Opioid Use. (OPIO2)

Opioid Physiology and Individual Outcomes With Supplemental O₂ (OPIO2)

This study will evaluate whether supplemental oxygen given during sleep improves breathing stability and sleep-disordered breathing in adults who use prescription opioids long term.

Participants will receive both supplemental oxygen and sham air during separate overnight sleep studies in a randomized order. The two study conditions will be separated by a washout period of approximately one week. Researchers will compare breathing during sleep with supplemental oxygen versus sham air and will also evaluate measures of oxygen levels, carbon dioxide levels, sleep quality, alertness, and other aspects of breathing and sleep.

For participants who previously took part in the GENESIS study, qualifying assessments from that study may be used to meet certain baseline requirements when appropriate, which may reduce the need to repeat some testing.

Study Overview

• Status: Not yet recruiting
• Conditions: Sleep-disordered Breathing; Chronic Opioid Use
• Intervention / Treatment: Other: Sham Air; Drug: Supplemental Oxygen

Detailed Description

This is a Phase II, single-center, randomized, double-blind, sham-controlled crossover study evaluating the effects of nocturnal supplemental oxygen on ventilatory stability and sleep-disordered breathing in adults receiving chronic opioid therapy.

Eligible participants will be randomized to one of two treatment sequences: supplemental oxygen followed by sham air, or sham air followed by supplemental oxygen. Each intervention will be administered during a separate in-laboratory overnight polysomnography (PSG) visit, with an approximately 1-week washout period between intervention nights. Each participant will therefore receive both study conditions and serve as their own control.

The study will evaluate the effect of supplemental oxygen on flow-based apnea-hypopnea index (AHIflow) and other measures of respiratory physiology, sleep-disordered breathing, oxygenation, carbon dioxide levels, neurobehavioral performance, and patient-reported sleep outcomes.

Most participants are expected to have previously enrolled in the GENESIS study (IRB #814091). When appropriate, qualifying assessments previously completed through GENESIS may be used to satisfy corresponding OPIO2 baseline requirements. OPIO2 informed consent, confirmation of current eligibility, and any required missing or repeat assessments must be completed before randomization.

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pamela N De Young, RPSGT; Phone Number: 858-232-0343; Email: pdeyoung@health.ucsd.edu
• Study Contact Backup: Name: Stacie L Moore, CRT-SDS; Phone Number: 6197356727; Email: s3moore@health.ucsd.edu

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Altman Clinical and Translational Research Institute
      • Contact: Bernadette e Cale, RN, MSN; Phone Number: (858)-822-1717; Email: bcale@health.ucsd.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 to 75 years.
• Chronic opioid use for ≥3 months with a daily opioid dose equivalent to at least 20 mg of oral morphine (morphine equivalent daily dose [MEqD]). Examples include approximately 13 mg oxycodone, 20 mg hydrocodone, 100 mg tramadol, or equivalent doses of other opioids.
• Ability and willingness to comply with study procedures, including overnight laboratory polysomnography and administration of oxygen or sham air in the laboratory.
• Ability to provide written informed consent.
• For participants able to become pregnant: agreement to use an effective contraceptive method (e.g., a licensed hormonal or intrauterine method, or an effective barrier method) during study participation. The study team will review and document the method before enrollment.
• Recruitment will target approximately equal numbers of males and females to enable consideration of sex as a biological variable, consistent with NIH policy.

In addition to the enrollment criteria, participants must meet the following criterion to be eligible for randomization:

• Diagnosis of sleep-disordered breathing (SDB), defined as AASM-recommended apnea-hypopnea index (AHI3A) ≥5 events per hour on a qualifying sleep study. AHI3A includes hypopnea definition ≥30% airflow reduction lasting ≥10 seconds, accompanied by ≥3% SpO2 desaturation or arousal.

Exclusion Criteria:

• Body mass index (BMI) >35 kg/m².
• Requirement for supplemental oxygen therapy outside of the study.
• Current use of CPAP or other sleep-apnea treatment that cannot safely be withheld during OPIO2 research PSG nights.
• Known severe pulmonary disease (e.g., advanced chronic obstructive pulmonary disease) that, in the opinion of the investigator, may increase the risk of oxygen-induced hypercapnia.
• Unstable or clinically significant cardiopulmonary disease, including but not limited to decompensated heart failure, unstable angina, or clinically significant arrhythmia.
• Recent hospitalization (within the past 30 days) or anticipated need for hospitalization during the study period.
• Recreational or non-prescribed opioid use.
• Alcohol use exceeding 2 standard drinks per day or evidence of substance use disorder that may interfere with study participation.
• Presence of other sleep disorders or neurologic conditions that significantly affect breathing during sleep (e.g., neuromuscular disease), in the opinion of the investigator.
• Pregnancy or breastfeeding, or planning to become pregnant during the study period.
• Positive pregnancy test at screening (serum or urine) for participants able to become pregnant. A pregnancy test will be repeated before each awake chemoreflex session or in-laboratory PSG visit; one same-day test may cover both; a positive test triggers withdrawal from further study procedures.
• Hospitalization for respiratory failure within the prior 12 months.
• Severe untreated insomnia (Insomnia Severity Index >22) likely to preclude completion of in-laboratory PSG visits.
• Inability to communicate in English sufficient for informed consent and study procedures, where a qualified interpreter consistent with UCSD HRPP policy is not available.
• Inability to tolerate nasal cannula or study procedures.
• Inability to provide informed consent or comply with study procedures.
• Any medical, psychiatric, or social condition that, in the opinion of the investigator, would interfere with safe participation or interpretation of study results.
• Prisoners or individuals who are involuntarily incarcerated.
• Inability or unwillingness to comply with research-center oxygen-safety precautions, including restrictions on smoking, vaping, open flames, and other ignition sources near oxygen equipment.

In addition to the enrollment exclusion criteria, participants will be excluded from randomization if the following criterion is met:

• Evidence of significant hypercapnia, defined as transcutaneous carbon dioxide (TcCO2) >55 mmHg for >10 minutes during baseline polysomnography (PSG).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sham Air Followed by Supplemental Oxygen; Participants will receive sham air during the first in-laboratory overnight polysomnography (PSG) visit, followed by an approximately 1-week washout period, and then receive supplemental oxygen during the second in-laboratory overnight PSG visit.	Other: Sham Air; Sham air will be delivered during sleep through a nasal cannula using a standard wall air flow controller during an in-laboratory overnight polysomnography (PSG). Sham air will be delivered at a fixed flow rate of 4 L/min and may be reduced to 3 L/min for participant comfort.; Drug: Supplemental Oxygen; Supplemental oxygen will be delivered during sleep through a nasal cannula using a standard wall oxygen flow controller during an in-laboratory overnight polysomnography (PSG). Supplemental oxygen will be delivered at a fixed flow rate of 4 L/min and may be reduced to 3 L/min for participant comfort.
Experimental: Supplemental Oxygen Followed by Sham Air; Participants will receive supplemental oxygen during the first in-laboratory overnight polysomnography (PSG) visit, followed by an approximately 1-week washout period. Participants will then receive sham air during the second in-laboratory overnight PSG visit.	Other: Sham Air; Sham air will be delivered during sleep through a nasal cannula using a standard wall air flow controller during an in-laboratory overnight polysomnography (PSG). Sham air will be delivered at a fixed flow rate of 4 L/min and may be reduced to 3 L/min for participant comfort.; Drug: Supplemental Oxygen; Supplemental oxygen will be delivered during sleep through a nasal cannula using a standard wall oxygen flow controller during an in-laboratory overnight polysomnography (PSG). Supplemental oxygen will be delivered at a fixed flow rate of 4 L/min and may be reduced to 3 L/min for participant comfort.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow-Based Apnea-Hypopnea Index (AHIflow)	AHIflow is the number of apneas lasting at least 10 seconds plus airflow-reduction events with a greater than 30% reduction in airflow lasting at least 10 seconds, divided by total sleep time in hours. Each respiratory event is counted once. Oxygen desaturation or arousal is not required. AHIflow will be measured during each intervention PSG, and the primary treatment comparison will be the within-participant difference between the supplemental oxygen and sham air conditions.	During each overnight intervention PSG, approximately 1 week apart

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Loop Gain	Loop gain is a dimensionless measure of ventilatory control instability estimated from overnight polysomnography (PSG) data. Loop gain will be assessed during each intervention PSG to evaluate the effect of supplemental oxygen compared with sham air on ventilatory control.	During each overnight intervention PSG, approximately 1 week apart

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Jeremy Orr, MD, University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: October 16, 2026
• First Submitted That Met QC Criteria: November 2, 2026
• First Posted (Actual): November 6, 2026

Study Record Updates

• Last Update Posted (Actual): November 6, 2026
• Last Update Submitted That Met QC Criteria: November 2, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Obstructive Sleep Apnea; Polysomnography; Sleep-Disordered Breathing; Central Sleep Apnea; Supplemental Oxygen; Nocturnal Hypoxemia; Chronic Opioid Use; Ventilatory Instability; Loop Gain
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Sleep Apnea, Central
• Other Study ID Numbers: 814959; R01HL179220 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

De-identified individual participant data generated under this protocol may be shared with collaborators or repositories, as permitted by the informed consent document, UC San Diego IRB/HRPP requirements, NIH/NHLBI data-sharing requirements, institutional policy, and applicable data-use agreements. Shared datasets will not include direct identifiers unless specifically approved by the IRB/HRPP and permitted by the informed consent document.

IPD Sharing Time Frame

Beginning after publication of the primary study results and available thereafter in accordance with NIH/NHLBI data-sharing requirements and applicable institutional policies.

IPD Sharing Access Criteria

Qualified researchers may request access to de-identified individual participant data for research purposes. Access will be provided only as permitted by the informed consent document, UC San Diego IRB/HRPP requirements, NIH/NHLBI data-sharing requirements, institutional policy, and applicable data-use agreements. Shared datasets will not include direct identifiers unless specifically approved by the IRB/HRPP and permitted by the informed consent document.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No