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

Sponsor

University of Athens (Other)

Overall Status

Unknown status

CT.gov ID

NCT01188005

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obstructive Sleep Apnea Syndrome	Device: n-CPAP Device: Oxygen supplementation Drug: Vitamin A, Vitamin C, Vitamin E, Allopurinol, N-Acetylcysteine	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

Aug 1, 2010

Anticipated Primary Completion Date :

Oct 1, 2010

Anticipated Study Completion Date :

Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Device: n-CPAP administration of continuous positive airway pressure through a nasal device 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
No Intervention: 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.

Arm

Intervention/Treatment

Experimental: 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

Device: n-CPAP

administration of continuous positive airway pressure through a nasal device

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

No Intervention: 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.

Outcome Measures

Primary Outcome Measures

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

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