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

Obstructive Sleep Apnea Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01188005
• Other study ID #: 439
• Status: Recruiting
• Phase: N/A
• First received: August 20, 2010
• Last updated: August 24, 2010
• Start date: August 2010
• Est. completion date: October 2010

Study information

• Verified date: August 2010
• Source: University of Athens
• Contact: Georgios K Prezerakos, MD
• Phone: 00306946337935
• Email: gprezerak[@]yahoo.com
• Is FDA regulated: No
• Health authority: Greece: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea Syndrome
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive
• Syndrome

Intervention

Device:
• n-CPAP
administration of continuous positive airway pressure through a nasal device
• Oxygen supplementation
Oxygen supplementation (3L) through nasal spectacles

Drug:
• 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

Locations

Country	Name	City	State
Greece	Department of Critical Care Evangelismos General Hospital	Athens	Attiki

Sponsors (1)

Lead Sponsor	Collaborator
University of Athens

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	TNF-a area under the curve	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	three months	No