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

NCT01188005 | Unknown DMC

• 1 other identifier: 439
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Keywords

OSAS; Sleep Apnoea; IL6; TNFα; Oxidative Stress; Antioxidants

Outcome Measures

Primary Outcomes (1)

• IL-6 Area under the curve

  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

  three months

Secondary Outcomes (1)

• TNF-a area under the curve

  three months

Study Arms (2)

OSAS patients

EXPERIMENTAL

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

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

Control Group

NO INTERVENTION

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.

Interventions

n-CPAP DEVICE

administration of continuous positive airway pressure through a nasal device

OSAS patients

Oxygen supplementation DEVICE

Oxygen supplementation (3L) through nasal spectacles

OSAS patients

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

OSAS patients

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Obstructive Sleep Apnea Syndrome diagnosis

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Athens: lead

Study Sites (1)

Department of Critical Care Evangelismos General Hospital

Athens, Attica, Greece

RECRUITING

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Sleep Apnea Syndromes

Interventions

Vitamin A; Ascorbic Acid; Vitamin E; Allopurinol; Acetylcysteine

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Carbohydrates; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Purines; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Theodoros Vassilakopoulos, MD, PhD

  Associate Professor in Critical Care, University of Athens

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Georgios K Prezerakos, MD

CONTACT

00306946337935; gprezerak@yahoo.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 20, 2010
• First Posted: August 25, 2010
• Study Start: August 1, 2010
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: August 25, 2010

Record last verified: 2010-08

Locations

GR (1)