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

National and Kapodistrian University of Athens

Status: Unknown

Conditions: Obstructive Sleep Apnea Syndrome

Treatments: Device: Oxygen supplementation; Device: n-CPAP; Drug: Vitamin A, Vitamin C, Vitamin E, Allopurinol, N-Acetylcysteine

Study type: Interventional

Funder types: Other

Identifiers

NCT01188005

439

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

OSAS patients

Experimental group

Description:

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

Treatment:

Device: Oxygen supplementation

Drug: Vitamin A, Vitamin C, Vitamin E, Allopurinol, N-Acetylcysteine

Device: n-CPAP

Control Group

No Intervention group

Description:

This group is scheduled to undergo a plain polysomnographic study, whilst plasma cytokine levels will be measured. It will comprise of healthy, non-OSAS volunteers.