Clinical trial NCT01188005: Inflammatory Mediators in Obstructive Sleep Apnoea Syndrome; Mechanisms of Production and the Effect of Long Term Antioxidants Administration
Official title: Inflammatory Mediators in Obstructive Sleep Apnoea Syndrome; Mechanisms of Production and the Effect of Long Term Antioxidants Administration
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obstructive Sleep Apnea Syndrome
Keywords: OSAS
Sleep Apnoea
IL6
TNFα
Oxidative Stress
Antioxidants
Lead sponsor: University of Athens
Sponsor class: OTHER
First posted: 2010-08-25
Enrollment: 30
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: IL-6 Area under the curve
timeFrame: three months
Secondary outcomes:
measure: TNF-a area under the curve
timeFrame: three months
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Department of Critical Care Evangelismos General Hospital
state: Attiki
Study officials:
affiliation: Associate Professor in Critical Care, University of Athens
name: Theodoros Vassilakopoulos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: