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Vascular Pathophysiology in Obstructive Sleep Apnea

This study has been withdrawn prior to enrollment.
Information provided by (Responsible Party):
University of Wisconsin, Madison Identifier:
First received: September 13, 2005
Last updated: October 6, 2015
Last verified: October 2015
Obstructive sleep apnea (OSA) is a medical problem whose importance is increasing in recognition and awareness. The National Commission on Sleep Disorders estimates that 15 million Americans have OSA, many of whom remain undiagnosed (24). OSA is associated with the development of hypertension and other cardiovascular diseases (1,2). Patients with OSA, like those with congestive heart failure, hypertension, hypercholesterolemia and diabetes, exhibit impaired EDV (25-32). OSA is also associated with impairments in endothelium-dependent cerebral blood flow responses, which may be a risk factor for stroke (33). Impaired EDV is a result of reduced production or inadequate action of nitric oxide. Since EDV worsens with disease progression and improves with disease treatment, it serves as a prognostic marker of vascular function (34-37). In OSA, hypoxia and neurohumoral disturbances increase generation of reactive oxygen species (ROS) that neutralize nitric oxide and impair endothelium-dependent responses (9,10,38). One source of ROS in endothelial cells is the enzyme xanthine oxidase (38). XO is an enzyme present in the vascular endothelium that significantly contributes to generation of ROS in congestive heart failure, hypercholesterolemia and diabetes (13-17). Inhibition of XO improves endothelium-dependent resistance vessel responses in these populations (13-17), but it is unknown if XO significantly contributes to oxidative stress and endothelial dysfunction in OSA. The central hypothesis of this application is that inhibition of XO with allopurinol will reduce oxidative stress and generation of ROS, thereby improving nitric oxide bioavailability and EDV in OSA. Our hypothesis has been formulated on the basis that patients with OSA experience repeated hypoxemia that increases activity of XO and other enzymes, thus increasing the generation of ROS that negatively impact EDV. Hypoxia is detrimental to vascular homeostasis since it increases generation of ROS through direct mechanisms and via activation of XO.

Condition Intervention
Obstructive Sleep Apnea
Drug: Allopurinol

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double-Blind
Official Title: Influence of Xanthine Oxidase Inhibition on Vascular Function in Obstructive Sleep Apnea

Resource links provided by NLM:

Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Forearm resistance ratios between the infused and non-infused arms at the highest dose of acetylcholine (30 mcg/minute)

Secondary Outcome Measures:
  • Area under the curve in reduction of forearm resistance during acetylcholine following allopurinol compared to placebo

Enrollment: 0

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Patients with Sleep Disordered Breathing:
  • Significant obstructive sleep apnea as verified by complete overnight polysomnography with apnea-hypopnea index (AHI) > 10 events per hour.
  • Fasting total cholesterol < 240 mg/dL
  • Fasting blood glucose < 120 mg/dL
  • Control subjects:
  • Free of sleep disordered breathing verified by complete overnight polysomnography or oxygen desaturation screening (AHI < 5 events per hour)
  • Fasting total cholesterol < 240 mg/dL
  • Fasting blood glucose < 120 mg/dL

Exclusion Criteria:

  • Presence of any cardiovascular diseases or medical conditions that will affect vascular responses (other than sleep apnea)
  • Subject taking any vasoactive medications, willing to stop taking vitamins or supplements for study participation
  • Current smokers
  • History of adverse reaction to allopurinol, acetylcholine, nitroprusside, verapamil or lidocaine
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Please refer to this study by its identifier: NCT00214084

United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
University of Wisconsin, Madison
Principal Investigator: John M Dopp, PharmD University of Wisconsin, Madison
  More Information

Responsible Party: University of Wisconsin, Madison Identifier: NCT00214084     History of Changes
Other Study ID Numbers: 2003-085
Study First Received: September 13, 2005
Last Updated: October 6, 2015

Additional relevant MeSH terms:
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Nervous System Diseases
Molecular Mechanisms of Pharmacological Action
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Free Radical Scavengers
Protective Agents
Physiological Effects of Drugs processed this record on April 21, 2017