Vascular Endothelial Dysfunction in Sleep Apnea
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Columbia University
- Enrollment
- 110
- Locations
- 1
- Primary Endpoint
- Circulating levels of Angiopoietin-2 after 4 weeks of atorvastatin vs. placebo therapy
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Active drug and placebo will be made identical in appearance and given to participants in a blinded fashion.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Treatment
OSA patients who adhered or did not adhere with CPAP who are randomized to receive atorvastatin 10 mg daily.
Intervention: Atorvastatin 10mg (Drug)
Treatment
OSA patients who adhered or did not adhere with CPAP who are randomized to receive atorvastatin 10 mg daily.
Intervention: Continuous Positive Airway Pressure Therapy (Other)
Control
OSA patients who adhered or did not adhere with CPAP who are randomized to receive placebo daily.
Intervention: Placebo (Drug)
Control
OSA patients who adhered or did not adhere with CPAP who are randomized to receive placebo daily.
Intervention: Continuous Positive Airway Pressure Therapy (Other)
Outcomes
Primary Outcomes
Circulating levels of Angiopoietin-2 after 4 weeks of atorvastatin vs. placebo therapy
Time Frame: 4 weeks post-treatment
Mean circulating levels of Ang-2 will be quantified after 4 weeks of statin or placebo therapy by enzyme-linked immunosorbent assay (ELISA)
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
Time Frame: 4 weeks post-treatment
Mean Interactions ER-bound VAPB with late endosome-bound ORP1L in harvested endothelial cells (ECs) will be assessed using proximity ligation assay (DuoLink, fluorescence area in µm2) after 4 weeks of atorvastatin or placebo therapy
Secondary Outcomes
- Endothelial cell free cholesterol levels after 4 weeks of atorvastatin vs. placebo(4 weeks post-treatment)
- Circulating levels of von Willebrand factor cleavage products after 4 weeks of atorvastatin vs. placebo(4 weeks post-treatment)
- Circulating levels of von Willebrand factor (vWF) cleavage products (low, medium, high molecular weight) at baseline and after 4 weeks of CPAP(4 weeks post-CPAP)
- Endothelial cell lipid droplets after 4 weeks of atorvastatin vs. placebo(4 weeks post-treatment)
- 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(4 weeks post-CPAP)
- Endothelial cell nuclear factor kappa B (NF-κB) nuclear fluorescence intensity after 4 weeks of atorvastatin vs. placebo(4 weeks post-treatment)
- Circulating levels of E-selectin after 4 weeks of atorvastatin vs. placebo therapy(4 weeks post-treatment)
- Endothelial cell messenger ribonucleic acid (mRNA) expression of EC adhesion molecules after 4 weeks of atorvastatin vs. placebo(4 weeks post-treatment)
- Endothelial cell interactions between CD59 and Weibel Palade Bodies (WPBs) after 4 weeks of atorvastatin vs. placebo(4 weeks post-treatment)
- Circulating levels of Angiopoietin-2 at baseline and after 4 weeks of CPAP therapy(4 weeks post-CPAP)
Investigators
Sanja Jelic
Associate Professor of Medicine
Columbia University