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

Inflammation Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01312168
• Other study ID #: 201012085RB
• Status: Active, not recruiting
• Phase: N/A
• First received: March 8, 2011
• Last updated: December 12, 2016
• Start date: March 2011
• Est. completion date: February 2017

Study information

• Verified date: December 2016
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Ministry of Health and Welfare
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 30 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Apnea
• Continuous Positive Airway Pressure
• Endothelium
• Inflammation
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive
• Vascular Diseases
• Vascular Function

Intervention

Device:
• Therapeutic CPAP
CPAP ventilator, optimal pressure decided by CPAP manual titration, daily use at sleep, six months
• Subtherapeutic CPAP
Subtherapeutic CPAP ventilator, pressure <3 cmH2O, daily use at sleep, six months

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (2)

Lead Sponsor	Collaborator
National Taiwan University Hospital	China Medical University, China

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	vascular reactivity of brachial artery and pulse wave velocity		six months	No
Secondary	percentage of adhesion molecule expression on monocytes		six months	No
Secondary	levels of extra and intracellular cytokine		six months	No