Recruiting
Phase 2

Observational Study

Sponsor:

UCLA

Code:

NCT05237505

Conditions

Obstructive Sleep Apnea

Chronic Obstructive Pulmonary Disease

Overlap Syndrome

Eligibility Criteria

Sex: All

Age: 40 - 70+

Healthy Volunteers: Not accepted

Interventions

bi-level positive pressure non invasive ventilation

Oxygen gas

Study Details

Brief summary:

Major progress has been made in the area of cardiovascular disease, but we believe that further progress will involve mechanistically addressing underlying respiratory causes including chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA). The most common cause of death in COPD is cardiovascular, although mechanisms are unknown. OSA has been associated with major neurocognitive and cardiovascular sequelae, the latter likely a function of autonomic nervous system abnormalities, oxidative stress, inflammation, and other pathways. Recent data suggest that individuals with OVS die preferentially of cardiovascular disease compared to OSA or COPD alone, although mechanisms are again unclear.

The combination of OSA and COPD may lead to profound hypoxemia. Individuals with COPD can develop pulmonary hypertension via disturbances in gas exchange and parenchymal injury leading to loss of pulmonary vasculature. OSA has been associated with mild to moderate pulmonary hypertension, but the situation may be worse if combined with parenchymal lung disease. The biological response to sustained hypoxemia has been carefully studied as has the topic of intermittent hypoxemia; however, to our knowledge, very little research has occurred regarding the combination of sustained plus intermittent hypoxia as seen in OVS. For example, we do not really know whether individuals with OVS develop coronary disease, right or left heart failure, dysrhythmias or some combination of abnormalities predisposing them to cardiovascular death. Thus, design of interventional studies is challenging as causal pathways are poorly understood despite our considerable preliminary data addressing these issues.

The purpose of this study is to examine vascular mechanisms in individuals with COPD/OSA overlap syndrome (OVS) compared with matched individuals with obstructive sleep apnea (OSA) alone or chronic obstructive pulmonary disease (COPD) alone and to perform a phase II pilot mechanistic clinical trial in OVS to examine the effect size of nocturnal bi-level positive airway pressure (PAP) vs. nocturnal oxygen therapy in cardiovascular outcomes.

Conditions

Obstructive Sleep Apnea

Chronic Obstructive Pulmonary Disease

Overlap Syndrome

Study ID

NCT05237505

Start date

Feb 13, 2024

Status verified date

Jun, 2026

Completion date

Aug 31, 2028

Anticipated

Primary completion date

Aug 31, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 40 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Provision of signed and dated informed consent form.
  • Stated willingness to comply with all study procedures and availability for the duration of the study.
  • Persons aged 40-79.
  • For women, only postmenopausal women will be included
  • Diagnosed with untreated moderate to severe obstructive sleep apnea (apnea-hypopnea index ≥15 events/hr and ≤80 events/hr) and/or diagnosed with COPD with FEV1/FVC ratio <0.7 and will be on stable medications as assessed by a board-certified pulmonologist.

Exclusion Criteria:

  • Premenopausal women (i.e. women are pregnant or may become pregnant) or lactation
  • Presence of specific devices: cardiac implantable electronic device (CIED) such as pacemakers, implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT) devices, metallic foreign bodies, implantable neurostimulation systems, cochlear implants/ear implant, drug infusion pumps (insulin delivery, analgesic drugs, or chemotherapy pumps), metallic fragments such as bullets, shotgun pellets, and metal shrapnel , cerebral artery aneurysm clips, magnetic dental implants, and artificial limb.
  • Known allergic reactions to components of the study intervention: (if getting contrast, MRI contrast (gadolinium)).
  • Concurrent severe sleep disorders (such as periodic limb movements, restless legs syndrome, narcolepsy, idiopathic hypersomnia, etc).
  • Exhibit Cheyne-Stokes respiration or central sleep apnea (> 25 % of events central)
  • Take potentially confounding medications or hormones that affect breathing.
  • Subjects will be excluded if they are deemed medically unstable with active neurological, cardiac, liver, endocrine, and infectious diseases.
  • We will also exclude participants with pulmonary disease apart from COPD.
  • We will exclude participants with active cancer treatment.
  • We will exclude azotemia (estimated glomerular fraction rate < 30ml/min) as there is some concern about giving gadolinium to these patients (if getting contrast MRI).
  • people with exposures deemed to be problematic for the research e.g. any smoking in bedroom by participant or household member, major second-hand smoke, e-cigarettes, tetrahydrocannabinol, major drug or alcohol consumption (>3 oz/day) and other environmental pollution effects (indoor and outdoor).
  • Individuals who are already on continuous O2 for COPD or PAP treatment for OSA.
  • Patients with sustained desaturations below 89% during wake time will be excluded for ethical reasons since withholding oxygen in hypoxemic patients would be at odds with standard of care.
  • Individuals with OSA (AHI range 15-80/hr) will be screened for pathological sleepiness and will be excluded if ESS >18/24, history of motor vehicle accident or near miss accident, or high-risk occupation.
  • COPD individuals with arterial PCO2 higher than 52 mmHg will be excluded.
  • Individuals who are currently incarcerated.

Study Design

Enrollment

240 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Oxygen

OVS subjects will receive treatment with oxygen during night time for 6 months

experimental: Bi-level positive pressure non invasive ventilation

OVS subjects will receive treatment with bi-level PAP therapy during night time for 6 months

Interventions

bi-level positive pressure non invasive ventilation

Participants randomized to the bi-level arm will be provided with an auto bi-level device that automatically delivers the required pressure. The settings in the auto bi-level will be minimum EPAP of 4 cmH2O, maximum IPAP of 24 cmH2O, and a range of pressure support between 6-10 cmH2O. For those participants who have been randomized to the bi-level group but have not successfully acclimated to the device with the automatic bi-level settings, we will conduct an in-lab titration of the bi-level therapy during the optional Overnight visit 2.

Oxygen gas

The dose of nocturnal oxygen in all participants in the oxygen therapy arm will be 2 liters/minute. Patients with daytime hypoxemia, measured as sustained desaturations below 89% during wake time and/or arterial blood PO2 ≤ 55 mmHg, will be excluded from this study (as specified in the exclusion criteria) for ethical reasons since withholding oxygen in hypoxemic patients would be at odds with standard of care.

Primary outcome measure

  • Right ventricular mass [ Time Frame: 6 Months ]
  • Reactive Hyperemia Index [ Time Frame: 6 months ]
  • 5th generation troponin [ Time Frame: 6 months ]
  • MiR-210 [ Time Frame: 6 months ]

Central Contacts and Locations

Central contacts

Pamela DeYoung, BA

8582462183pdeyoung@health.ucsd.edu

Locations

UCSD Sleep Research

Recruiting

La Jolla, California, United States, 92037

Contacts

Pam DeYoung, RPSGT

858-246-2154sleepresearch@health.ucsd.edu

Pamela DeYoung, RPSGT

858 2462154pdeyoung@health.ucsd.edu

More Information

Sponsor

University of California, San Diego

Last update posted

Jun 3, 2026

Last verified

Jun, 2026

Keywords

  • OSA
  • obstructive sleep apnea
  • COPD
  • chronic obstructive pulmonary disease
  • PAP therapy
  • oxygen
  • cardiovascular health

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of California, San Diego on 2026-06-03.