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

NCT ID: NCT01188005

Last Updated: 2010-08-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2010-10-31

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.

Conditions

Obstructive Sleep Apnea Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

OSAS patients

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

Group Type: EXPERIMENTAL

n-CPAP

Intervention Type: DEVICE

administration of continuous positive airway pressure through a nasal device

Oxygen supplementation

Intervention Type: DEVICE

Oxygen supplementation (3L) through nasal spectacles

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

Intervention Type: DRUG

Vitamin A 50,000 IU, Vitamin C 1000 mg , Vitamin E 200 mg, Allopurinol 600 mg, N-Acetylcysteine 2 g. Duration is set for 60 days

Control Group

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

n-CPAP

administration of continuous positive airway pressure through a nasal device

Intervention Type: DEVICE

Oxygen supplementation

Oxygen supplementation (3L) through nasal spectacles

Intervention Type: DEVICE

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

Vitamin A 50,000 IU, Vitamin C 1000 mg , Vitamin E 200 mg, Allopurinol 600 mg, N-Acetylcysteine 2 g. Duration is set for 60 days

Intervention Type: DRUG

Eligibility Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Athens

OTHER

Sponsor Role: lead

Responsible Party

University of Athens Medical School

Principal Investigators

Theodoros Vassilakopoulos, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Associate Professor in Critical Care, University of Athens

Locations

Department of Critical Care Evangelismos General Hospital

Athens, Attica, Greece

Site Status: RECRUITING

Countries

Greece

Central Contacts

Georgios K Prezerakos, MD

Role: CONTACT

gprezerak@yahoo.com

00306946337935

Other Identifiers

439

Identifier Type: -

Identifier Source: org_study_id