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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2010 by University of Athens.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University of Athens
ClinicalTrials.gov Identifier:
NCT01188005
First received: August 20, 2010
Last updated: August 24, 2010
Last verified: August 2010
  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

Resource links provided by NLM:


Further study details as provided by University of Athens:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01188005

Contacts
Contact: Georgios K Prezerakos, MD 00306946337935 gprezerak@yahoo.com

Locations
Greece
Department of Critical Care Evangelismos General Hospital Recruiting
Athens, Attiki, Greece
Sponsors and Collaborators
University of Athens
Investigators
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
Vitamin A
Vitamins
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014