Study to Assess the Changes in Blood Clotting Factors and Blood Vessel Wall Function in Obstructive Sleep Apnea

August 19, 2013 updated by: Kanika Bagai, Vanderbilt University

Variability of Fibrinolytic Markers and Endothelial Function in Obstructive Sleep Apnea

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.

Study Overview

Status

Completed

Conditions

Obstructive Sleep Apnea

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.

Study Type

Observational

Enrollment (Actual)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Tennessee
  - Nashville, Tennessee, United States, 37232
    - Vanderbilt University Medical Center,Department of Neurology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

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).

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
Healthy controls 18 years or older with body mass index between 25-45
Obstructive Sleep Apnea Group Age 18 years or older with body mass index between 25 and 45

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparison of Levels of Mean PAI-1 Activity in Patients With Obstructive Sleep Apnea and Controls. Time Frame: at the initial visit	at the initial visit

Secondary Outcome Measures

Outcome Measure	Time Frame
Comparison of Endothelial (Blood Vessel) Wall Diameter in Patients With Obstructive Sleep Apnea Versus Controls. Time Frame: at initial visit	at initial visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University

Investigators

Principal Investigator: Kanika Bagai, M.D, Vanderbilt University Medical Center, Nashville, TN

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2008

Primary Completion (Actual)

April 1, 2012

Study Completion (Actual)