Inflammatory Mediators in Obstructive Sleep Apnoea Syndrome; Mechanisms of Production and the Effect of Long Term Antioxidants Administration
Recruitment status was Recruiting
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Purpose
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 | Intervention |
|---|---|
|
Obstructive Sleep Apnea Syndrome |
Device: n-CPAP Device: Oxygen supplementation Drug: Vitamin A, Vitamin C, Vitamin E, Allopurinol, N-Acetylcysteine |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Factorial Assignment Masking: 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 |
- IL-6 Area under the curve [ Time Frame: three months ] [ Designated as safety issue: No ]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
- TNF-a area under the curve [ Time Frame: three months ] [ Designated as safety issue: No ]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
| Estimated Enrollment: | 30 |
| Study Start Date: | August 2010 |
| Estimated Study Completion Date: | October 2010 |
| Estimated Primary Completion Date: | October 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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.
|
Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| Contact: Georgios K Prezerakos, MD | 00306946337935 | gprezerak@yahoo.com |
| Greece | |
| Department of Critical Care Evangelismos General Hospital | Recruiting |
| Athens, Attiki, Greece | |
| Principal Investigator: | Theodoros Vassilakopoulos, MD, PhD | Associate Professor in Critical Care, University of Athens |
More Information
No publications provided
| Responsible Party: | Associate Professor Theodoros Vassilakopoulos, University of Athens Medical School |
| ClinicalTrials.gov Identifier: | NCT01188005 History of Changes |
| Other Study ID Numbers: | 439 |
| Study First Received: | August 20, 2010 |
| Last Updated: | August 24, 2010 |
| Health Authority: | Greece: Ethics Committee |
Keywords provided by University of Athens:
|
OSAS Sleep Apnoea IL6 |
TNFα Oxidative Stress Antioxidants |
Additional relevant MeSH terms:
|
Apnea Sleep Apnea Syndromes Sleep Apnea, Obstructive Respiration Disorders Respiratory Tract Diseases Signs and Symptoms, Respiratory Signs and Symptoms Sleep Disorders, Intrinsic Dyssomnias Sleep Disorders Nervous System Diseases Acetylcysteine Allopurinol N-monoacetylcystine Antioxidants |
Ascorbic Acid Retinol palmitate Vitamin E Alpha-Tocopherol Tocopherols Tocotrienols Vitamin A Vitamins Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Expectorants Respiratory System Agents Free Radical Scavengers |
ClinicalTrials.gov processed this record on May 23, 2013