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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by National Taiwan University Hospital
Sponsor:
Collaborator:
China Medical University, China
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01312168
First received: March 8, 2011
Last updated: October 30, 2013
Last verified: October 2013
  Purpose

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

Condition Intervention
Sleep Apnea, Obstructive
Continuous Positive Airway Pressure
Endothelium
Inflammation
Vascular Function
Device: Therapeutic CPAP
Device: Subtherapeutic CPAP

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

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • vascular reactivity of brachial artery and pulse wave velocity [ Time Frame: six months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • percentage of adhesion molecule expression on monocytes [ Time Frame: six months ] [ Designated as safety issue: No ]
  • levels of extra and intracellular cytokine [ Time Frame: six months ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: March 2011
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   30 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01312168

Contacts
Contact: Peilin Lee, M.D. 886-223562755 leepeilin@ntu.edu.tw

Locations
Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Peilin Lee, M.D.    886-223562755    leepeilin@ntu.edu.tw   
Sponsors and Collaborators
National Taiwan University Hospital
China Medical University, China
Investigators
Principal Investigator: Peilin Lee, M.D. National Taiwan University Hospital
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01312168     History of Changes
Other Study ID Numbers: 201012085RB
Study First Received: March 8, 2011
Last Updated: October 30, 2013
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
Cardiovascular disease
Continuous positive airway pressure
Endothelium
Vascular function
Inflammation
Sleep Apnea
Obstructive

Additional relevant MeSH terms:
Inflammation
Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Vascular Diseases
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on October 01, 2014