The Cardiovascular Consequences of Sleep Apnea Plus COPD (Overlap Syndrome)
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age40-79
SponsorUniversity of California, San Diego
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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).
Trial design
Design model
Parallel
Treatments tested in this trial
bi-level positive pressure non invasive ventilation
DeviceParticipants 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
DrugThe 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.
Treatment groups
240 Participants
are divided into 2 treatment groupsGroup A: OxygenExperimental treatment 1 intervention
Group B: Bi-level positive pressure non invasive ventilationExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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
Time frame
6 Months2
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.
Time frame
6 months3
5th generation troponin
Troponin will be measured from participant serum samples. Troponin is a marker of myocardial injury.
Time frame
6 months4
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
Time frame
6 monthsSecondary outcomes
1
Verbal Paired-Associates task
Participants will complete a word pairs task, which is a computerized memory assessment designed to prime participants to memorize 26 pairs of words in the evening. To assess sleep-dependent memory consolidation, recall of these word pairs are tested in the morning after the overnight sleep study.
Time frame
6 months2
Response Speed
Objective assessment of brain function will be done using 10-minute psychomotor vigilance test
Time frame
6 monthsSponsors and contacts
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Source ClinicalTrials.gov