Clinical trial NCT00936481: Study to Assess the Changes in Blood Clotting Factors and Blood Vessel Wall Function in Obstructive Sleep Apnea
Official title: Variability of Fibrinolytic Markers and Endothelial Function in Obstructive Sleep Apnea
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obstructive Sleep Apnea
Keywords: OSA
Lead sponsor: Vanderbilt University
Sponsor class: OTHER
First posted: 2009-07-10
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: We are looking for adults over age 18 years without significnt medical or psychiatric conditions (other than sleep apnea).

Brief summary: Obstructive sleep apnea is a condition in which people have decreased breathing during their sleep. Untreated sleep apnea has been linked to increased risk for cardiovascular diseases.

This research study is looking at blood clotting factors and blood vessel function in health volunteers and patients with newly diagnosed or untreated obstructive sleep apnea to better understand the underlying mechanisms for increased cardiovascular risk.

Detailed description: Cardiovascular disease (CVD), which includes strokes, has been the number one killer in the United States.Each year about 700,000 people experience a new or recurrent stroke, which translates into about one stroke every 45 seconds. Apart from traditional risk factors for stroke such as hypertension, smoking and atrial fibrillation, obstructive sleep apnea is now being increasingly recognized as another important treatable risk factor.

The majority of strokes and myocardial infarctions are due to atherothrombotic events. Impaired fibrinolytic activity increases the propensity for thromboembolic events. Many different candidate molecules have been studied as the cause of a hypercoagulable state. Plasminogen Activator Inhibitor-1 (PAI-1) is the major physiologic inhibitor of the body's fibrinolytic system including the principal serine protease tissue-type plasminogen activator (t-PA). It is therefore poised to be a pivotal regulator of the fibrinolytic system.Recent studies have shown that PAI-1 levels are elevated in patients with obstructive sleep apnea (OSA) and that PAI-1 levels correlate with severity of OSA.

The purpose of this pilot study is twofold:

* To characterize changes in the blood levels of plasminogen activator inhibitor-1 (PAI-1) and tissue type plasminogen activator ( t-PA) across the 24 hour cycle in patients with obstructive sleep apnea, as compared to normal controls, and to further identify the pattern of changes with varying severity of obstructive sleep apnea, and
* To study endothelial function in patients with obstructive sleep apnea, as compared to normal controls.

Data gathered from this pilot study will be used to initiate a more comprehensive prospective study exploring the link between OSA, endothelial function, the fibrinolytic system and cardiovascular events. This area can be further explored by prospectively following patients to assess for a reduction in such events with treatment of OSA.

Eligibility criteria: Inclusion Criteria:

* Age 18 years or older.
* Subjects are able and willing to provide informed consent.
* Subjects are willing to cooperate with polysomnography and have serial blood draws over a 24-hour period.
* Evidence for OSA (AHI\>5 events/hour) without treatment or suspected OSA based on symptoms in the patient group.
* Body mass index of 25-45

Exclusion Criteria:

* History of myocardial infarction, stroke or transient ischemic attack (TIA) or peripheral vascular disease.
* History of chronic diseases such as diabetes mellitus, uncontrolled hypertension (SBP \>160, DBP \> 120), renal failure on dialysis, cancer, autoimmune or liver disease.
* A significant history of medical or psychiatric disease that may impair participation in the trial.
* Evidence of medical instability (cardiac arrhythmias, congestive heart failure, pulmonary disease) that require an expedited evaluation and treatment of the OSA.
* History of alcohol, or drug abuse during the one-year-period prior to trial participation.
* Current use of tobacco products.
* Current treatment with angiotensin converting enzyme-inhibitors and or chronic use of non-steroidal anti-inflammatory agents.
* Another primary sleep disorder that requires intervention with medications or cause disrupted sleep.
* Patients with unusual sleep or wake habits, including shift work.
* Transmeridian travel in the previous 3 months.
* Patients with OSA who have already received treatment with CPAP, surgery or oral appliance.
* Pregnancy; as hormonal changes affect sleep disordered breathing.

Primary outcomes:
measure: Comparison of Levels of Mean PAI-1 Activity in Patients With Obstructive Sleep Apnea and Controls.
timeFrame: at the initial visit
Secondary outcomes:
measure: Comparison of Endothelial (Blood Vessel) Wall Diameter in Patients With Obstructive Sleep Apnea Versus Controls.
timeFrame: at initial visit
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center,Department of Neurology
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center, Nashville, TN
name: Kanika Bagai, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005 Nov 10;353(19):2034-41. doi: 10.1056/NEJMoa043104.