Clinical trial NCT05289063: Vascular Endothelial Dysfunction in Sleep Apnea
Official title: Vascular Endothelial Dysfunction in Sleep Apnea
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Obstructive Sleep Apnea of Adult
Keywords: CPAP
Atorvastatin
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2022-03-21
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized double blind design
Primary purpose: BASIC_SCIENCE

Brief summary: This double-blind placebo-controlled parallel group randomized study design will be used to test whether 4 weeks of atorvastatin 10 mg daily reduces levels of inflammatory markers in OSA patients treated with CPAP (standard of care). The purpose of this study is to investigate: 1) whether statins reduce endothelial inflammation and pro-thrombotic conditions in OSA, including in patients adherent to CPAP (Aim 1); and 2) whether statins reduce endothelial inflammation and pro-thrombotic conditions by improving endothelial cholesterol metabolism and trafficking in OSA (Aim 2).

Detailed description: Obstructive sleep apnea (OSA), a condition that affects a quarter of American adults, triples the risk for cardiovascular diseases and increases all-cause mortality. Standard therapy with continuous positive airway pressure (CPAP) does not improve cardiovascular risk. Based on the investigators' mechanistic observation that the abnormal cycle of endothelial inflammation can be disrupted with statin therapy, the investigators now propose randomized clinical trial of statins vs. placebo to determine its effects on endothelial dysfunction in OSA patients treated with CPAP, which may provide the basis for practical clinical trials of statins for reducing cardiovascular risk in OSA.

Eligibility criteria: Inclusion Criteria:

* Aged ≥18 years
* Newly diagnosed with obstructive sleep apnea (OSA) who were never treated with CPAP. OSA is defined as apnea-hypopnea index (AHI) ≥5 events/hour of sleep.

Exclusion Criteria:

* A history of coronary artery disease, heart failure, stroke, diabetes, malignancy, chronic pulmonary, kidney or rheumatologic disease, muscle pain/fatigue, smoking within the past 5 years
* Regular use of any medications

Primary outcomes:
measure: Circulating levels of Angiopoietin-2 after 4 weeks of atorvastatin vs. placebo therapy
timeFrame: 4 weeks post-treatment
measure: Interaction of endoplasmic reticulum (ER)-bound vesicle-associated membrane protein-associated protein B (VAPB) with late endosome-bound ORP1L (proximity ligation assay fluorescence area in µm2) after 4 weeks of atorvastatin vs. placebo therapy
timeFrame: 4 weeks post-treatment
Secondary outcomes:
measure: Circulating levels of von Willebrand factor cleavage products after 4 weeks of atorvastatin vs. placebo
timeFrame: 4 weeks post-treatment
measure: Circulating levels of von Willebrand factor (vWF) cleavage products (low, medium, high molecular weight) at baseline and after 4 weeks of CPAP
timeFrame: 4 weeks post-CPAP
measure: Endothelial cell free cholesterol levels after 4 weeks of atorvastatin vs. placebo
timeFrame: 4 weeks post-treatment
measure: Endothelial cell lipid droplets after 4 weeks of atorvastatin vs. placebo
timeFrame: 4 weeks post-treatment
measure: Endothelial cell interactions between CD59 and Weibel Palade Bodies (WPBs) after 4 weeks of atorvastatin vs. placebo
timeFrame: 4 weeks post-treatment
measure: Circulating levels of Angiopoietin-2 at baseline and after 4 weeks of CPAP therapy
timeFrame: 4 weeks post-CPAP
measure: Interaction of ER-bound VAPB with late endosome-bound ORP1L (proximity ligation assay fluorescence area in µm2) at baseline and after 4 weeks of CPAP therapy
timeFrame: 4 weeks post-CPAP
measure: Endothelial cell nuclear factor kappa B (NF-κB) nuclear fluorescence intensity after 4 weeks of atorvastatin vs. placebo
timeFrame: 4 weeks post-treatment
measure: Circulating levels of E-selectin after 4 weeks of atorvastatin vs. placebo therapy
timeFrame: 4 weeks post-treatment
measure: Endothelial cell messenger ribonucleic acid (mRNA) expression of EC adhesion molecules after 4 weeks of atorvastatin vs. placebo
timeFrame: 4 weeks post-treatment
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Sanja Jelic, MD
role: PRINCIPAL_INVESTIGATOR
References: