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

NCT ID: NCT01312168

Last Updated: 2016-12-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2017-02-28

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.

Conditions

Sleep Apnea, Obstructive; Continuous Positive Airway Pressure; Endothelium; Inflammation; Vascular Function

Keywords

Cardiovascular disease; Continuous positive airway pressure; Endothelium; Vascular function; Inflammation; Sleep Apnea; Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Healthy non-OSA control

Group Type: NO_INTERVENTION

No interventions assigned to this group

OSA receiving therapeutic CPAP

Group Type: EXPERIMENTAL

Therapeutic CPAP

Intervention Type: DEVICE

CPAP ventilator, optimal pressure decided by CPAP manual titration, daily use at sleep, six months

OSA receiving subtherapeutic CPAP

Group Type: SHAM_COMPARATOR

Subtherapeutic CPAP

Intervention Type: DEVICE

Subtherapeutic CPAP ventilator, pressure \<3 cmH2O, daily use at sleep, six months

Interventions

Therapeutic CPAP

CPAP ventilator, optimal pressure decided by CPAP manual titration, daily use at sleep, six months

Intervention Type: DEVICE

Subtherapeutic CPAP

Subtherapeutic CPAP ventilator, pressure \<3 cmH2O, daily use at sleep, six months

Intervention Type: DEVICE

Eligibility Criteria

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

• 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
• sleepy driver
• using maintenance medications

Control subjects

• 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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

China Medical University, China

OTHER

Sponsor Role: collaborator

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peilin Lee, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

National Taiwan University Hospital

Taipei, , Taiwan

Countries

Taiwan

Other Identifiers

201012085RB

Identifier Type: -

Identifier Source: org_study_id