The Cardiovascular Consequences of Sleep Apnea Plus COPD (Overlap Syndrome)

NCT05237505 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 808025
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Right ventricular mass

  Cardiac magnet resonance imaging (CMRI): All subjects will undergo cardiac MRI measurements the same day they undergo the evaluation of vascular reactivity measurements. Supine cardiac MRI imaging will be performed using a 3T MR scanner (GE 750, GE Healthcare) with a 16-element cardiac coil for radiofrequency signal reception. Non-invasive blood pressure will be monitored during cardiac MRI scanning (Dinemap). Standard and novel MRI sequences will be used for myocardial tissue characterization, assessment of ventricular function, pulmonary hemodynamics, and aortic compliance

  6 Months

• Reactive Hyperemia Index

  Based on a device called EndoPAT, which measures non-invasively bloodflow before, during, and after 5-minutes of occlusion to one arm.

  6 months

• 5th generation troponin

  Troponin will be measured from participant serum samples. Troponin is a marker of myocardial injury.

  6 months

• MiR-210

  MicroRNA-210 will be measured from participant serum samples. miR210 may predict risk of atherosclerosis and changes in levels may give insight into mechanisms of our interventions

  6 months

Secondary Outcomes (2)

• Verbal Paired-Associates task

  6 months

• Response Speed

  6 months

Study Arms (2)

Oxygen

EXPERIMENTAL

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

Drug: Oxygen gas

Bi-level positive pressure non invasive ventilation

EXPERIMENTAL

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

Device: bi-level positive pressure non invasive ventilation

Interventions

bi-level positive pressure non invasive ventilation DEVICE

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.

Also known as: Auto-bilevel, BIPAP, Non invasive ventilation

Bi-level positive pressure non invasive ventilation

Oxygen gas DRUG

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.

Also known as: O2

Oxygen

Eligibility Criteria

• Age: 40 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

UCSD Sleep Research

La Jolla, California, 92037, United States

RECRUITING

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Pulmonary Disease, Chronic Obstructive

Interventions

Noninvasive Ventilation; nitrox

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Lung Diseases, Obstructive; Lung Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy

Study Officials

• Atul Malhotra, MD

  UCSD

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pamela DeYoung, BA

CONTACT

8582462183; pdeyoung@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Investigator and Outcomes Assessor
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Medicine

Model Details: 6-month, 2-arm randomized, parallel, interventional mechanistic study of COPD/OSA overlap syndrome to compare bi-level PAP vs. O2 therapy Qualified participants will be randomized to receive either O2 therapy or bi-level therapy.

Study Record Dates

• First Submitted: February 2, 2022
• First Posted: February 14, 2022
• Study Start: February 13, 2024
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)