Inflammatory Mediators in Obstructive Sleep Apnoea Syndrome; Mechanisms of Production and the Effect of Long Term Antioxidants Administration

Not Applicable

• Conditions: Obstructive Sleep Apnea Syndrome
• Interventions: Device: n-CPAP; Device: Oxygen supplementation; Drug: Vitamin A, Vitamin C, Vitamin E, Allopurinol, N-Acetylcysteine

• Registration Number: NCT01188005
• Lead Sponsor: University of Athens

Brief Summary

Obstructive Sleep Apnea Syndrome (OSAS) is associated with elevated plasma levels of IL-6 and TNF-α, which cannot be accounted for by obesity (Vgontzas et al Sleep Med Rev 2005;9:211-24, Ciftci et al Cytokine 2004;28:87-91\].

Obstructive apneas-hypopneas are accompanied by strenuous diaphragmatic contractions before the ensuing arousals and re-establishment of airway patency. We have shown that strenuous diaphragmatic contractions induced by resistive loading lead to elevated plasma levels of IL-6, TNF-α, and IL-1β (Vassi-lakopoulos et al AJRCCM 2002;166:1572-8) with concomitant up-regulation of the cytokines within the diaphragmatic myofibers (Vassilakopoulos et al AJRCCM 2004;170:154-61).

OSAS patients exhibit frequent episodes of hypoxemia during the night. Loaded breathing is a form exercise for the respiratory muscles, and both acute and chronic hypoxia lead to an augmented plasma IL-6 response to exercise compared to normoxia (Lundby et al Eur J Appl Physiol 2004;91:88-93).

In OSAS, monocytes have oxidative stress (Dyugovskaya et al AJRCCM 2002;165:934-9) and produce more cytokines (TNF-α) in vitro (Minoguchi et al Chest 204;126:1473-9).

Hypothesis #1: plasma levels of IL-6 and TNF-α are increased during the night in OSAS patients secondary to the intermittent strenuous diaphragmatic contractions and the episodes of hypoxia-reoxygenation associated with the obstructive apneas-hypopneas.

Hypothesis #2: monocytes from sleep apnea patients, exhibit augmented intracellular expression of IL-6 and TNF-α during the night.

Hypothesis #3: Oxidative stress is a stimulus for cytokine upregulation in OSAS.

Detailed Description

Not available

Study Timeline

• Status Verified: 2010-08
• Study Start: 2010-08
• Study First Submitted: 2010-08-20
• Study First Submitted QC: 2010-08-24
• Last Update Submitted: 2010-08-24
• Study First Posted: 2010-08-25
• Last Update Posted: 2010-08-25
• Primary Completion: 2010-10
• Study Completion: 2010-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Obstructive Sleep Apnea Syndrome diagnosis

Exclusion Criteria

• narcolepsy or idiopathic hypersomnia
• chronic obstructive disease,
• neuromuscular or endocrinological disease,
• autoimmune systemic disease,
• psychological disorders,
• use of non steroids antinflammatory drugs,
• use of cortisone drugs,
• recent or concomitant systemic infections
• upper or lower airway infections

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
OSAS patients	n-CPAP	This arm includes the OSAS diagnosed cohort that has been planned to undergo four polysomnographic studies. One standard, one with oxygen supplementation, one with n-CPAP device and one post antioxidants administration
OSAS patients	Oxygen supplementation	This arm includes the OSAS diagnosed cohort that has been planned to undergo four polysomnographic studies. One standard, one with oxygen supplementation, one with n-CPAP device and one post antioxidants administration
OSAS patients	Vitamin A, Vitamin C, Vitamin E, Allopurinol, N-Acetylcysteine	This arm includes the OSAS diagnosed cohort that has been planned to undergo four polysomnographic studies. One standard, one with oxygen supplementation, one with n-CPAP device and one post antioxidants administration

Primary Outcome Measures

Name	Time	Method
IL-6 Area under the curve	three months	The primary outcome measure ( IL-6 Area under the curve) is evaluated at the end of each polysonographic study. We anticipate each subject to have completed all three sudies within one month and receive the antioxidant supplementation for an additional 60 day period. In total three months

Secondary Outcome Measures

Name	Time	Method
TNF-a area under the curve	three months	The secondary outcome measure ( TNF-a Area under the curve) is evaluated at the end of each polysonographic study. we anticipate each subject to have completed all three sudies within one month and receive the antioxidant supplementation for an additional 60 day period. In total three months

Trial Locations

Locations (1)

Department of Critical Care Evangelismos General Hospital; 🇬🇷 Athens, Attiki, Greece