Clinical trial NCT01312168: Endothelial Dysfunction, Monocyte Activation, and Vasculopathy in Patients With Obstructive Sleep Apnea (OSA) and Effect of 6-month CPAP Treatment
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
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
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
Collaborators: name: China Medical University, China
First posted: 2011-03-10
Enrollment: 150
Sex: MALE
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: vascular reactivity of brachial artery and pulse wave velocity
timeFrame: six months
Secondary outcomes:
measure: percentage of adhesion molecule expression on monocytes
timeFrame: six months
measure: levels of extra and intracellular cytokine
timeFrame: six months
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Peilin Lee, M.D.
role: PRINCIPAL_INVESTIGATOR
References: