Effect of Selective and Nonselective Cyclooxygenase Enzyme Inhibition on Arterial Blood Pressure and Cerebral Blood Flow With Exposure to Intermittent Hypoxia in Humans

Study Overview
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Brief Summary
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The study has been designed to assess the effect of cyclooxygenase inhibition on blood pressure, cerebral blood flow, ventilation and renal hemodynamics following chronic intermittent hypoxia exposure.

Detailed Description
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The study will specifically evaluate: Cardiovascular effect of cyclooxygenase inhibitors on cerebral, vascular, blood pressure and homeostatic responses following chronic intermittent hypoxia exposure. Ventilatory response of cyclooxygenase inhibitors following chronic intermittent hypoxia exposure Evaluate the renal hemodynamic effect of chronic intermittent hypoxia exposure and cyclooxygenase inhibition.

Official Title
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Effect of Selective and Nonselective Cyclooxygenase Enzyme Inhibition on Arterial Blood Pressure and Cerebral Blood Flow With Exposure to Intermittent Hypoxia in Humans

Conditions
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Obstructive Sleep Apnea, Hypertension, Cardiovascular Diseases, Stroke

Intervention / Treatment
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* Other: Intermittent hypoxia
* Drug: Indomethacin
* Drug: Celecoxib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects 18 - 45 years of age Informed written consent Exclusion Criteria: Any history of cardio-respiratory diseases, ongoing medication, smoking, trauma, acute illnesses, collagen vascular diseases, rheumatoid arthritis, osteoarthritis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Intermittent hypoxia|The subjects will receive five days of drug intervention: either non-selective cyclooxygenase (Indomethacin) or selective cyclooxygenase-2 inhibition (Celecoxib) or placebo. On the testing day, the subjects will undergo an acute intermittent hypoxia testing before and six hours of hypoxic chamber exposure mimicking obstructive sleep apnea syndrome.|
|Drug: Indomethacin|The subjects will receive five days of drug intervention: either non-selective cyclooxygenase (Indomethacin) or selective cyclooxygenase-2 inhibition (Celecoxib) or placebo. Then they will be tested with an exposure of intermittent hypoxia. Indomethacin: 50 mg, Oral, three times per day for five days.|
|Drug: Celecoxib|The subjects will receive five days of drug intervention: either non-selective cyclooxygenase (Indomethacin) or selective cyclooxygenase-2 inhibition (Celecoxib) or placebo. Then they will be tested with an exposure of intermittent hypoxia. Celecoxib: 200 mg, Oral, two times per day for five days with a visually matching sequential placebo in between of two doses.|
|Drug: Placebo|The subjects will receive five days of drug intervention: either non-selective cyclooxygenase (Indomethacin) or selective cyclooxygenase-2 inhibition (Celecoxib) or placebo. Then they will be tested with an exposure of intermittent hypoxia. Placebo: Oral, three times per day for five days.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterial Blood Pressure | Blood pressure will be monitored during all three protocols. | Six weeks | 
| Cerebral Blood Flow | The cerebral blood flow will be mesauresed during each testing days of all three protocols. | Six weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilatory Response | The ventilatory response will be measured during each testing days of all three protocols. | Six weeks. | 
| Renal Hemodynamics | The renal hemodynamics will be measured during each testing days of all three protocols. | Six weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obstructive Sleep Apnea, Hypoxia, Sleep, Blood Pressure, Hypertension, Myocardial Infarction, Stroke, Ventilation, Brain, Cerebral Blood Flow, Renal Blood Flow