Endothelial Damage and Atherosclerosis in Obstructive Sleep Apnea

• ClinicalTrials.gov Identifier: NCT00942643
• Recruitment Status: Terminated
• First Posted: July 21, 2009
• Last Update Posted: July 4, 2012
• Sponsor: The University of Hong Kong
• Information provided by (Responsible Party): Lam Jamie Chung Mei, The University of Hong Kong

Tracking Information

• First Submitted Date: July 20, 2009
• First Posted Date: July 21, 2009
• Last Update Posted Date: July 4, 2012
• Study Start Date: May 2008
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 20, 2009): AGEs levels [ Time Frame: 4 weeks and 12 weeks ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: July 20, 2009): endothelial function as assessed by reactive hyperemia-induced peripheral arterial tone response [ Time Frame: 4 weeks and 12 weeks ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Endothelial Damage and Atherosclerosis in Obstructive Sleep Apnea
• Official Title: Endothelial Damage and Atherosclerosis in Obstructive Sleep Apnea: the Role of Advanced Glycation End-products

Brief Summary

The investigators hypothesize that obstructive sleep apnea (OSA) may lead to increased formation/accumulation of advanced glycation ends (AGEs), and that the increase in AGEs is contributed in part by increased insulin resistance. The investigators further hypothesize that AGEs contribute to vascular endothelial damage and ultimately atherosclerosis in OSA.

The objectives of this study are:

1. To explore the relationship between insulin resistance and AGEs in OSA
2. To study the relationship between AGE and vascular endothelial dysfunction in OSA
3. To study the relationship between AGE and early atherosclerosis in OSA

Detailed Description

There is growing evidence to suggest that pathophysiology of OSA may lead to atherosclerosis, independent of confounding variables which are often present in these subjects with OSA. Many mechanisms have been reported to contribute to vasculopathy in OSA, but whether increased AGEs formation contribute significantly to the pathogenesis of cardiovascular morbidity in OSA remains to be determined.

Advanced glycation product is formed by non-enzymatic reaction of reducing sugars such as glucose with the amino groups of proteins, and subsequent glycoxidation. AGEs can form on long-lived extracellular proteins as well as short-lived molecules, cytoplasmic proteins and nuclear acids. AGEs cause a number of adverse cellular events and they have been demonstrated in fatty streaks and atherosclerotic plaques. The formation and tissue accumulation of AGE is shown to be enhanced by hyperglycemia and/or increased oxidative stress. There is increasing evidence to support this as an important mechanism of vascular and other end organ damage in diabetes and some other diseases. In OSA, there is evidence to support an increased insulin resistance and excessive oxidative stress, both of which may predispose to AGE formation. We have preliminary data to suggest increased levels of circulating AGE in non-diabetic OSA subjects. Since insulin resistance with elevated blood glucose levels, albeit not up to diabetic thresholds, may partially contribute to increase in AGE.

Many potential mechanisms of atherosclerosis have been reported, but direct evidence for atherosclerosis is still lacking. Subjects with OSA also have comorbidities which may give rise to atherosclerosis. With the advancement of non-invasive techniques for detection of vascular endothelial damage and early atherosclerosis, it is possible to detect early vascular abnormalities in otherwise healthy OSA subjects. This hypothesis underlies our objectives to explore the relationship between AGE and the markers of endothelial dysfunction and early atherosclerosis. Some of these early changes, especially at endothelial level, may be reversible if the insult of OSA is removed. Thus a longitudinal comparison of OSA-treated and OSA-untreated subjects on such changes would further help to clarify the issue.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Investigator); Primary Purpose: Treatment

Condition

• Obstructive Sleep Apnea
• Insulin Resistance
• Endothelial Function
• Oxidative Stress

Intervention

Device: CPAP machine

a machine delivers positive airway pressure into the upper airway via a nasal mask

Other Name: Continuous Positive Airway Pressure

Study Arms

• No Intervention: no treatment
  being observed at 4 weeks and 12 weeks
• Active Comparator: CPAP treatment
  a machine delivers positive airway pressure into the upper airway via nasal mask
  Intervention: Device: CPAP machine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 3, 2012): 10
• Original Estimated Enrollment (submitted: July 20, 2009): 50
• Actual Study Completion Date: March 2010
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• age 18-65 years old
• AHI >= 15
• BMI < 35

Exclusion Criteria:

• Known cardiovascular disease, including hypertension
• Diabetes
• Acute or unstable chronic disease
• Renal failure
• Major organ system failure, including liver, renal, cardiac and respiratory failure
• Taking long-term medications

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Hong Kong

Administrative Information

• NCT Number: NCT00942643
• Other Study ID Numbers: HKCTR-772
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Lam Jamie Chung Mei, The University of Hong Kong
• Study Sponsor: The University of Hong Kong
• Collaborators: Not Provided

Investigators

• Principal Investigator: Mary SM Ip, MD; Queen Mary Hospital, The University of Hong Kong

• PRS Account: The University of Hong Kong
• Verification Date: July 2012