Vascular Endothelial Dysfunction in Sleep Apnea

NCT05289063 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: AAAT88102R01HL106041
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

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).

Conditions

Obstructive Sleep Apnea of Adult

Keywords

CPAP; Atorvastatin

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (10)

• 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 free cholesterol levels after 4 weeks of atorvastatin vs. placebo

  4 weeks post-treatment

• Endothelial cell lipid droplets 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

Study Arms (2)

Treatment

ACTIVE COMPARATOR

OSA patients who adhered or did not adhere with CPAP who are randomized to receive atorvastatin 10 mg daily.

Drug: Atorvastatin 10mg; Other: Continuous Positive Airway Pressure Therapy

Control

PLACEBO COMPARATOR

OSA patients who adhered or did not adhere with CPAP who are randomized to receive placebo daily.

Drug: Placebo; Other: Continuous Positive Airway Pressure Therapy

Interventions

Atorvastatin 10mg DRUG

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.

Also known as: statin

Treatment

Placebo DRUG

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.

Control

Continuous Positive Airway Pressure Therapy OTHER

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.

Also known as: CPAP

Control; Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Columbia University: lead

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Interventions

Atorvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses

Study Officials

• Sanja Jelic, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sanja Jelic, MD

CONTACT

2125438875; sj366@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Active drug and placebo will be made identical in appearance and given to participants in a blinded fashion.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: Randomized double blind design

Study Record Dates

• First Submitted: March 10, 2022
• First Posted: March 21, 2022
• Study Start: October 3, 2022
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)