Vascular Endothelial Dysfunction in Sleep Apnea

Obstructive Sleep Apnea of Adult Clinical Trial

Official title:

Vascular Endothelial Dysfunction in Sleep Apnea

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05289063
• Other study ID #: AAAT8810
• Secondary ID: 2R01HL106041
• Status: Recruiting
• Phase: Phase 1
• Start date: October 3, 2022
• Est. completion date: February 28, 2026

Study information

• Verified date: February 2024
• Source: Columbia University
• Contact: Sanja Jelic, MD
• Phone: 2125438875
• Email: sj366[@]cumc.columbia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: February 28, 2026
• Est. primary completion date: February 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea of Adult
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• Atorvastatin 10mg
Atorvastatin 10 mg daily for 28 days will be randomly allocated to OSA patients regardless of adherence with CPAP. Atorvastatin and placebo will be encapsulated to appear identical and dispensed by the research pharmacy.
• Placebo
Placebo daily for 28 days will be randomly allocated to OSA patients regardless of adherence with CPAP. Atorvastatin and placebo will be encapsulated to appear identical and dispensed by the research pharmacy.

Other:
• Continuous Positive Airway Pressure Therapy
CPAP is a standard of care for OSA and will be prescribed by care providers not associated with this study based on clinical indications. The investigators will have no role in prescribing CPAP.

Locations

Country	Name	City	State
United States	Columbia University Irving Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Circulating levels of Angiopoietin-2 after 4 weeks of atorvastatin vs. placebo therapy	Mean circulating levels of Ang-2 will be quantified after 4 weeks of statin or placebo therapy by enzyme-linked immunosorbent assay (ELISA)	4 weeks post-treatment
Primary	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	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	4 weeks post-treatment
Secondary	Circulating levels of von Willebrand factor cleavage products after 4 weeks of atorvastatin vs. placebo	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	4 weeks post-treatment
Secondary	Circulating levels of von Willebrand factor (vWF) cleavage products (low, medium, high molecular weight) at baseline and after 4 weeks of CPAP	Mean Circulating levels (count) of vWF cleavage products (LMW, IMW, HMW) at baseline and after CPAP.	4 weeks post-CPAP
Secondary	Endothelial cell free cholesterol levels after 4 weeks of atorvastatin vs. placebo	Mean Endothelial cell free cholesterol levels (fluorescence intensity) after 4 weeks of atorvastatin vs. placebo therapy	4 weeks post-treatment
Secondary	Endothelial cell lipid droplets after 4 weeks of atorvastatin vs. placebo	Mean Endothelial cell lipid droplets (fluorescence area µm2) after 4 weeks of atorvastatin vs. placebo	4 weeks post-treatment
Secondary	Endothelial cell interactions between CD59 and Weibel Palade Bodies (WPBs) after 4 weeks of atorvastatin vs. placebo	Mean Endothelial cell interactions between CD59 and Weibel Palade Bodies (fluorescence area µm2) after 4 weeks of atorvastatin vs. placebo	4 weeks post-treatment
Secondary	Circulating levels of Angiopoietin-2 at baseline and after 4 weeks of CPAP therapy	Mean Circulating levels of Angiopoietin-2 after 4 weeks of CPAP therapy quantified by ELISA	4 weeks post-CPAP
Secondary	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	Mean Interaction of ER-bound VAPB with late endosome-bound ORP1L (proximity ligation assay fluorescence area in µm2) after 4 weeks of CPAP therapy	4 weeks post-CPAP
Secondary	Endothelial cell nuclear factor kappa B (NF-?B) nuclear fluorescence intensity after 4 weeks of atorvastatin vs. placebo	Mean Endothelial cell NF-kB nuclear fluorescence intensity after 4 weeks of atorvastatin vs. placebo	4 weeks post-treatment
Secondary	Circulating levels of E-selectin after 4 weeks of atorvastatin vs. placebo therapy	Mean Circulating levels of E-selectin after 4 weeks of atorvastatin vs. placebo therapy quantified by ELISA	4 weeks post-treatment
Secondary	Endothelial cell messenger ribonucleic acid (mRNA) expression of EC adhesion molecules after 4 weeks of atorvastatin vs. placebo	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)	4 weeks post-treatment