Vascular Endothelial Dysfunction in Sleep Apnea

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.
• Другое 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.

Первичные конечные точки

• Circulating levels of Angiopoietin-2 after 4 weeks of atorvastatin vs. placebo therapy [Срок оценки: 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 [Срок оценки: 4 weeks post-treatment]

Вторичные конечные точки (10)

• Circulating levels of von Willebrand factor cleavage products after 4 weeks of atorvastatin vs. placebo [Срок оценки: 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 [Срок оценки: 4 weeks post-CPAP]
• Endothelial cell free cholesterol levels after 4 weeks of atorvastatin vs. placebo [Срок оценки: 4 weeks post-treatment]
• Endothelial cell lipid droplets after 4 weeks of atorvastatin vs. placebo [Срок оценки: 4 weeks post-treatment]
• Endothelial cell interactions between CD59 and Weibel Palade Bodies (WPBs) after 4 weeks of atorvastatin vs. placebo [Срок оценки: 4 weeks post-treatment]
• Circulating levels of Angiopoietin-2 at baseline and after 4 weeks of CPAP therapy [Срок оценки: 4 weeks post-CPAP]
• 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 [Срок оценки: 4 weeks post-CPAP]
• Endothelial cell nuclear factor kappa B (NF-κB) nuclear fluorescence intensity after 4 weeks of atorvastatin vs. placebo [Срок оценки: 4 weeks post-treatment]
• Circulating levels of E-selectin after 4 weeks of atorvastatin vs. placebo therapy [Срок оценки: 4 weeks post-treatment]
• Endothelial cell messenger ribonucleic acid (mRNA) expression of EC adhesion molecules after 4 weeks of atorvastatin vs. placebo [Срок оценки: 4 weeks post-treatment]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Фундаментальное исследование

Центры проведения

США · 1 центр

• Columbia University Irving Medical Center — New York

Идентификаторы

NCT: NCT05289063 · AAAT8810 · 2R01HL106041

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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