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

Endothelial Dysfunction, Monocyte Activation, and Vasculopathy in Patients With Obstructive Sleep Apnea and Effect of Six-month CPAP Treatment: A Large-scale, Double-blind, Randomized, Placebo-controlled Trial

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

Study Overview

• Status: Unknown
• Conditions: Sleep Apnea, Obstructive; Inflammation; Vascular Function; Continuous Positive Airway Pressure; Endothelium
• Intervention / Treatment: Device: Therapeutic CPAP; Device: Subtherapeutic CPAP

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 Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

OSA patients

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Healthy non-OSA control
Experimental: OSA receiving therapeutic CPAP	Device: Therapeutic CPAP; CPAP ventilator, optimal pressure decided by CPAP manual titration, daily use at sleep, six months
Sham Comparator: OSA receiving subtherapeutic CPAP	Device: Subtherapeutic CPAP; Subtherapeutic CPAP ventilator, pressure <3 cmH2O, daily use at sleep, six months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
vascular reactivity of brachial artery and pulse wave velocity	six months

Secondary Outcome Measures

Outcome Measure	Time Frame
percentage of adhesion molecule expression on monocytes	six months
levels of extra and intracellular cytokine	six months

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: China Medical University, China
• Investigators: Principal Investigator: Peilin Lee, M.D., National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Anticipated): February 1, 2017
• Study Completion (Anticipated): February 1, 2017

Study Registration Dates

• First Submitted: March 8, 2011
• First Submitted That Met QC Criteria: March 9, 2011
• First Posted (Estimate): March 10, 2011

Study Record Updates

• Last Update Posted (Estimate): December 14, 2016
• Last Update Submitted That Met QC Criteria: December 12, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Inflammation; Sleep Apnea; Continuous positive airway pressure; Vascular function; Endothelium; Obstructive
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Inflammation; Apnea
• Other Study ID Numbers: 201012085RB