Preventive Effects of Bosentan on the Systemic Cardiovascular Consequence of Sleep Apnea

Study Overview
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Brief Summary
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The study will compared the effects of bosentan, an endothelin receptor antagonist, and nasal continuous positive airway pressure (nCPAP), obstructive sleep apnea current reference treatment, on diastolic blood pressure in untreated mildly hypertensive sleep apnea patients. The hypothesis is that blocking endothelin receptors with a drug will have the same systemic blood pressure lowering effect than nCPAP in sleep apnea patients.

Official Title
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Cardiovascular Consequences of Obstructive Sleep Apnea (OSA): Role of Endothelin and Preventive Effects of Bosentan

Conditions
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Obstructive Sleep Apnea, Hypertension

Intervention / Treatment
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* Drug: bosentan
* Device: nasal continuous positive airway pressure (CPAP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented obstructive sleep apnea with untreated mild systemic hypertension Exclusion Criteria: pregnancy or lactation daytime alveolar hypoventilation severe arterial hypertension (systolic pressure > 180 mmHg; diastolic pressure > 110 mmHg) treatment with anti-hypertensive drugs cardiovascular disorder other than mild hypertension severe daytime sleepiness (score on the EPWORTH sleepiness scale ≥15) or at-risk occupation contra-indication to nCPAP treatment known allergy to bosentan active treatment with a drug whose efficacy is reduced by cytochromes P450, 2C9, 3A4 and2C19 isoenzyme activation active treatment with a drug acting on systemic arterial blood pressure or endothelial function liver or kidney dysfunction

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: bosentan<br>* 62.5 mg b.i.d for 4 weeks<br>* Other names: TRACLEER;|
| Active Comparator: 2<br> | Device: nasal continuous positive airway pressure (CPAP)<br>* Daily application throughout sleep for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24 hour mean diastolic blood pressure |  | before and after each treatment completion (4 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peripheral Arterial Tonometry measure |  | before and after each treatment completion (4 weeks) | 
| mean 24 hour systemic systolic blood pressure |  | before and after each treatment completion (4 weeks) | 
| mean 24 hour nocturnal blood pressure |  | before and after each treatment completion (4 weeks) | 
| carotid Intima Media Thickness |  | before and after each treatment completion (4 weeks) | 
| Circulating inflammation markers (RANTES, MCP-1, TNF-alpha, INF-gamma, IL-6, IL-10 and TGF-gamma |  | before and after each treatment completion (4 weeks) | 
| Circulating Big ET1 and ET1 levels |  | before and after each treatment completion (4 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular system, Sleep, Endothelial function, Endothelin system