NCT05237505: CRESCENDO-SLP

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

Recruiting now Phase 2 Last updated 17 December 2025

What this trial tests

Phase 2 trial testing bi-level positive pressure non invasive ventilation in Obstructive Sleep Apnea in 240 participants. Currently enrolling.

Timeline

13 February 2024

Primary endpoint
31 August 2028

31 August 2028

Quick facts

Lead sponsor	University of California, San Diego
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	240
Start date	13 February 2024
Primary completion	31 August 2028
Estimated completion	31 August 2028
Sites	1 location across United States

Drugs / interventions tested

• bi-level positive pressure non invasive ventilation
• Oxygen gas — full drug profile →

Conditions studied

• Obstructive Sleep Apnea — all drugs for Obstructive Sleep Apnea →
• Chronic Obstructive Pulmonary Disease — all drugs for Chronic Obstructive Pulmonary Disease →
• Overlap Syndrome — all drugs for Overlap Syndrome →

Sponsor

University of California, San Diego

Who can join

Adults 40 to 79, any sex, with Obstructive Sleep Apnea or Chronic Obstructive Pulmonary Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Obstructive sleep apnea severity and pathophysiological traits in overlap syndrome: Insights from the SNOOzzzE cohort.
   Raphelson J, Sanchez-Azofra A, Orr JE, Parra G, et al · · 2025 · cited 2× · PMID 40611572 · DOI 10.14814/phy2.70438