Mechanism of Endothelial Dysfunction in Obstructive Sleep Apnea (OSA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Ohio State University
Sponsor:
Information provided by (Responsible Party):
Rami Khayat, The Ohio State University
ClinicalTrials.gov Identifier:
NCT01027078
First received: December 4, 2009
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

The investigators hypothesized that patients with Obstructive Sleep Apnea (OSA) who are free of any cardiovascular disease will have early microcirculatory changes that are unique to OSA, and therefore would resolve with treatment of OSA.


Condition
Obstructive Sleep Apnea

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Mechanism of Endothelial Dysfunction in Obstructive Sleep Apnea

Resource links provided by NLM:


Further study details as provided by Ohio State University:

Primary Outcome Measures:
  • eNOS Expression [ Time Frame: Measured at basline and 3-months post-treatment (CPAP) initiation ] [ Designated as safety issue: No ]
    All measurements will be obtained upon diagnosis of OSA and 12 weeks after effective treatment with continuous positive airway pressure (CPAP). Controls will receive all measurements at baseline.


Secondary Outcome Measures:
  • Peroxynitrite Formation [ Time Frame: Measured at basline and 3-months post-treatment (CPAP) initiation ] [ Designated as safety issue: No ]
    All measurements will be obtained upon diagnosis of OSA and 12 weeks after effective treatment with continuous positive airway pressure (CPAP). Controls will receive all measurements at baseline.


Other Outcome Measures:
  • Superoxide Production [ Time Frame: Measured at basline and 3-months post-treatment (CPAP) initiation ] [ Designated as safety issue: No ]
    All measurements will be obtained upon diagnosis of OSA and 12 weeks after effective treatment with continuous positive airway pressure (CPAP). Controls will receive all measurements at baseline.

  • Plasma BH2 and BH4 Levels [ Time Frame: Measured at basline and 3-months post-treatment (CPAP) initiation ] [ Designated as safety issue: No ]
    All measurements will be obtained upon diagnosis of OSA and 12 weeks after effective treatment with continuous positive airway pressure (CPAP). Controls will receive all measurements at baseline. The BH2/BH4 ratio will be measured using high pressure liquid chromatography (HPLC).

  • Plasma ADMA Levels [ Time Frame: Measured at basline and 3-months post-treatment (CPAP) initiation ] [ Designated as safety issue: No ]
    All measurements will be obtained upon diagnosis of OSA and 12 weeks after effective treatment with continuous positive airway pressure (CPAP). Controls will receive all measurements at baseline. Plasma ADMA levels will be measured using high pressure liquid chromatography (HPLC).


Biospecimen Retention:   Samples With DNA

skin biopsies


Estimated Enrollment: 72
Study Start Date: November 2009
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
OSA
patients diagnosed with obstructive sleep apnea who do not have existing cardiovascular disease
control
patients without obstructive sleep apnea who are matched in weight and age to the OSA patients

Detailed Description:

Impaired vascular regulation of the microcirculation is a consequence of Obstructive Sleep Apnea (OSA). Nitric Oxide (NO) related endothelial dysfunction occurs in OSA as the earliest vascular abnormality prior to the manifestation of vascular disease and it results in impaired vasodilatory response to hypoxia. These abnormalities have already been described in OSA patients. The role of oxidative stress in endothelial dysfunction is present in vascular disorders. The presence of oxidative stress in OSA patients is also well established. The effect of increased superoxide on endothelial function has also been described in the literature. The mechanism of this effect is unknown and is the focus of this research.

We hypothesized that patients with Obstructive Sleep Apnea (OSA) who are free of any cardiovascular disease will have early microcirculatory changes that are unique to OSA, and therefore would resolve with treatment of OSA.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Participants: will be 36 patients with newly diagnosed OSA and 36 age and BMI matched controls.

Patients with OSA will be enrolled from the sleep disorders center at OSU among patients who underwent a recent (past 4 weeks) polysomnography that is positive for OSA, and never were treated with CPAP.

Inclusion criteria will be AHI > 15 events per hours.

Criteria

Inclusion criteria:

1. Apnea-Hypopnea Index (AHI) > 15 events per hours.

Exclusion criteria:

  1. Hypertension defined by existing treatment with antihypertensives or any measurement of systolic pressure above 130 mmHg, or diastolic pressure above 85 mmHg;
  2. Dyslipidemia defined by fasting cholesterol above 200; or fasting LDL over 150 mg/dl;
  3. Diabetes defined as existing diagnosis, hemoglobin A1C >7 or fasting glucose >110 on two separate measurements (standard fasting glucose or HbA1C criteria);
  4. CAD defined by history of angina, coronary event or abnormal stress test;
  5. Peripheral Vascular Disease (PVD) defined by history of stroke, claudication or abnormal Ankle brachial index;
  6. Concurrent smoking;
  7. Pregnancy;
  8. Use of erectile dysfunction drugs, or any medications for chronic conditions; 9)Chronic liver or renal disease. Fasting blood test for glucose, cholesterol, on all participants who have not had these tests in the 6 month prior to enrollment, will be obtained at the time of screening. The remaining criteria will be evaluated by reviewing the medical records and history taking on the day of first visit.
  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: NCT01027078

Contacts
Contact: Brian Patt brian.patt@osumc.edu

Locations
United States, Ohio
The Davis Heart and Lung Research Institute Recruiting
Columbus, Ohio, United States, 43210
Contact: Brian Patt    614-292-0876    brian.patt@osumc.edu   
Sponsors and Collaborators
Rami Khayat
Investigators
Principal Investigator: Rami Khayat, MD Ohio State University
  More Information

No publications provided

Responsible Party: Rami Khayat, Associate Professor, The Ohio State University
ClinicalTrials.gov Identifier: NCT01027078     History of Changes
Other Study ID Numbers: 2009H0212
Study First Received: December 4, 2009
Last Updated: February 12, 2014
Health Authority: United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on July 26, 2014