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

November 2, 2026 updated by: Jeremy Orr, M.D., University of California, San Diego

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

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
62

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92037
        • Altman Clinical and Translational Research Institute
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Flow-Based Apnea-Hypopnea Index (AHIflow)
Time Frame: During each overnight intervention PSG, approximately 1 week apart

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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Loop Gain
Time Frame: During each overnight intervention PSG, approximately 1 week apart

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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of California, San Diego

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jeremy Orr, MD, University of California, San Diego

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2031

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 16, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 2, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 6, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 6, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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