Endothelial Dysfunction, Monocyte Activation, and Vasculopathy in Patients With Obstructive Sleep Apnea (OSA) and Effect of 6-month CPAP Treatment

Not Applicable

• Conditions: Inflammation; Continuous Positive Airway Pressure; Sleep Apnea, Obstructive; Vascular Function; Endothelium
• Interventions: Device: Therapeutic CPAP; Device: Subtherapeutic CPAP

• Registration Number: NCT01312168
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

This purpose of this study is to

1. Determine the change in endothelial dependent vascular reactivity and vascular properties

2. Determine the changes in monocytes activation

3. Determine the change in pro-inflammatory status

4. Investigate the effect of six-month CPAP therapy on the above changes in patients with OSA

Detailed Description

Obstructive sleep apnea (OSA), characterized with chronic intermittent hypoxia (CIH) and sleep fragmentation, is associated with three-fold higher risk of cardiovascular events. CIH could promote production of ROS which induced the adhesion of circulating monocytes, endothelium injury, and production of pro-inflammatory mediators and adhesion molecules and lead to formation of atherosclerotic plaque. Recent studies showed vascular endothelium function could be noninvasively assessed with Flow-mediated dilation (FMD) in brachial artery, whereas OSA patients have lower FMD compared to control subjects. However, the CPAP effects on vascular function have conflicting results. Conflicts usually involve the small sample size, lack of appropriate control, and inadequate control of confounding factors, like physical activity, and duration of CPAP treatment. Also, CPAP effect on other monocytes activation and inflammatory mediators are clear as well. Our previous studies showed 12-week CPAP treatment could not modify the levels of TNF-α and hsCRP. However, the 12-week treatment may be not long enough to draw the conclusions for benefit from long-term CPAP therapy. Therefore, we plan to conduct a cross-sectional followed by a double blind, randomized, placebo-control, parallel-group interventional study to prove our hypothesis that OSA can lead to endothelial dysfunction, monocytes activation, and pro-inflammatory state which leads to and vasculopathy and those changes can be reverted by CPAP.

Study Timeline

• Study Start: 2011-03
• Study First Submitted: 2011-03-08
• Study First Submitted QC: 2011-03-09
• Study First Posted: 2011-03-10
• Status Verified: 2016-12
• Last Update Submitted: 2016-12-12
• Last Update Posted: 2016-12-14
• Primary Completion: 2017-02
• Study Completion: 2017-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 150

Inclusion Criteria

• male patients aged 30 to 65 year who have daytime sleepiness (ESS>=10)
• newly diagnosed OSA (AHI>30/hr) by overnight PSG but never been treated

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Exclusion Criteria

• unwilling or unable to perform testing procedure
• past or current smoking history
• medical condition (including cardiovascular disease, chronic pulmonary disease, diabetes, endocrinologic disease, chronic renal failure, and psychiatric disease)
• systemic inflammatory conditions (system lupus erythematosus, rheumatoid arthritis, sarcoidosis, Crohn's disease, and ulcerative colitis)
• active neurologic event
• active infection two weeks prior to screening
• enrolled in other trials in the study period
• other sleep disorders
• sleepy driver
• using maintenance medications

Control subjects

Inclusion Criteria:

• Age-, sex-, body weight-, height-matched subjects with enrolled OSA patients
• non-sleepy
• no OSA confirmed by home sleep study (AHI<5/hr)

Exclusion Criteria:

• unwilling or unable to perform testing procedure
• past or current smoking history
• medical condition (including cardiovascular disease, chronic pulmonary disease, diabetes, endocrinologic disease, chronic renal failure, and psychiatric disease)
• systemic inflammatory conditions (system lupus erythematosus, rheumatoid arthritis, sarcoidosis, Crohn's disease, and ulcerative colitis)
• active neurologic event
• active infection two weeks prior to screening
• enrolled in other trials in the study period
• other sleep disorders
• using maintenance medications

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
OSA receiving therapeutic CPAP	Therapeutic CPAP	-
OSA receiving subtherapeutic CPAP	Subtherapeutic CPAP	-

Primary Outcome Measures

Name	Time	Method
vascular reactivity of brachial artery and pulse wave velocity	six months

Secondary Outcome Measures

Name	Time	Method
levels of extra and intracellular cytokine	six months
percentage of adhesion molecule expression on monocytes	six months

Trial Locations

Locations (1)

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan