Vascular Endothelial Dysfunction in Sleep Apnea
- Conditions
- Obstructive Sleep Apnea of Adult
- Interventions
- Registration Number
- NCT05289063
- Lead Sponsor
- Columbia University
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 110
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Atorvastatin 10mg OSA patients who adhered or did not adhere with CPAP who are randomized to receive atorvastatin 10 mg daily. Treatment Continuous Positive Airway Pressure Therapy OSA patients who adhered or did not adhere with CPAP who are randomized to receive atorvastatin 10 mg daily. Control Placebo OSA patients who adhered or did not adhere with CPAP who are randomized to receive placebo daily. Control Continuous Positive Airway Pressure Therapy OSA patients who adhered or did not adhere with CPAP who are randomized to receive placebo daily.
- Primary Outcome Measures
Name Time Method Circulating levels of Angiopoietin-2 after 4 weeks of atorvastatin vs. placebo therapy 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 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 Outcome Measures
Name Time Method Circulating levels of von Willebrand factor cleavage products after 4 weeks of atorvastatin vs. placebo 4 weeks post-treatment Mean Circulating levels (count) of von Willebrand factor (vWF) cleavage products (low molecular weight (LMW), medium molecular weight (IMW), high molecular weight (HMW)) after 4 weeks of atorvastatin vs. placebo
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 Mean Circulating levels (count) of vWF cleavage products (LMW, IMW, HMW) at baseline and after CPAP.
Endothelial cell free cholesterol levels after 4 weeks of atorvastatin vs. placebo 4 weeks post-treatment Mean Endothelial cell free cholesterol levels (fluorescence intensity) after 4 weeks of atorvastatin vs. placebo therapy
Endothelial cell lipid droplets after 4 weeks of atorvastatin vs. placebo 4 weeks post-treatment Mean Endothelial cell lipid droplets (fluorescence area µm2) after 4 weeks of atorvastatin vs. placebo
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 Mean Interaction of ER-bound VAPB with late endosome-bound ORP1L (proximity ligation assay fluorescence area in µm2) after 4 weeks of CPAP therapy
Endothelial cell nuclear factor kappa B (NF-κB) nuclear fluorescence intensity after 4 weeks of atorvastatin vs. placebo 4 weeks post-treatment Mean Endothelial cell NF-kB nuclear fluorescence intensity after 4 weeks of atorvastatin vs. placebo
Circulating levels of E-selectin after 4 weeks of atorvastatin vs. placebo therapy 4 weeks post-treatment Mean Circulating levels of E-selectin after 4 weeks of atorvastatin vs. placebo therapy quantified by ELISA
Endothelial cell messenger ribonucleic acid (mRNA) expression of EC adhesion molecules after 4 weeks of atorvastatin vs. placebo 4 weeks post-treatment Mean Endothelial cell mRNA expression of EC adhesion molecules after 4 weeks of atorvastatin vs. placebo quantified by reverse transcription polymerase chain reaction (RT-PCR)
Endothelial cell interactions between CD59 and Weibel Palade Bodies (WPBs) after 4 weeks of atorvastatin vs. placebo 4 weeks post-treatment Mean Endothelial cell interactions between CD59 and Weibel Palade Bodies (fluorescence area µm2) after 4 weeks of atorvastatin vs. placebo
Circulating levels of Angiopoietin-2 at baseline and after 4 weeks of CPAP therapy 4 weeks post-CPAP Mean Circulating levels of Angiopoietin-2 after 4 weeks of CPAP therapy quantified by ELISA
Trial Locations
- Locations (1)
Columbia University Irving Medical Center
🇺🇸New York, New York, United States