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Catecholamines Can Attenuate Intermittent Hypoxia-Induced Expression of TNF in Human Monocytes

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ClinicalTrials.gov Identifier: NCT00498862
Recruitment Status : Unknown
Verified September 2006 by National Taiwan University Hospital.
Recruitment status was:  Recruiting
First Posted : July 10, 2007
Last Update Posted : July 10, 2007
Sponsor:
Information provided by:
National Taiwan University Hospital

Brief Summary:

Specific aim To examine the effect of catecholamines on the modulation of intermittent hypoxia induced TNF- in human monocytes from both healthy subjects and OSA patients (2). To map the signaling pathway of catecholamines regulating the intermittent hypoxia induced TNF- expression.

(3). To explore the potential therapeutic effects of  or  agonists/antagonists on intermittent hypoxia induced TNF- expression


Condition or disease
Healthy

Detailed Description:

Obstructive sleep apnea syndrome (OSAS) is a common disease, which occurs in 4% middle-aged men and 2% middle-aged women. The characteristic of OSA is recurrent collapse of upper airway during sleep, which results in intermittent hypoxia and sympathetic activation. Cardiovascular complications associated with OSA include artherosclerosis, hypertension, coronary artery disease and congestive heart failure. Several inflammatory mediators including C-reactive protein (CRP), oxidative stress, adhesion molecules, vascular endothelial growth factor and proinflammatory cytokines, were found to be elevated in OSA, which attribute the developments of cardiovascular diseases in OSA. Our data showed serum levels of TNF were higher in OSA patients than in control subjects. And serum levels of TNF were inversely correlated with the lowest pulse oxygen saturation. After one-month CPAP treatment, serum of TNF could significantly go down. This finding suggested TNF was a good biomarker in studying OSA associated cardiovascular complications.

The presentations of sympathetic hyperactivity in OSA include hypercatecholaminemia and elevated sympathetic tone of peripheral nerve. Hypercatecholaminemia is known for attributing to the development of cardiovascular diseases. Our data showed plasma levels of both epinephrine and norepinephrine were higher in OSA patients than in control subjects. And the elevated catecholamine could go down after one-month CPAP treatment. Meanwhile, our data also showed the plasma levels of catecholamine were highly correlated with serum levels of TNF.

In vivo studies showed both epinephrine and norepinephrine could potentiate LPS-induced expression of TNF through 2 adrenergic receptors. However, the effect of catecholamine on TNF production in human monocytes in the hypoxic microenvironment has never been studied. Our preliminary data showed epinephrine had no effect on TNF expression in human monocyte cell line U937 under normoxic condition but could attenuate the TNF expression under hypoxic condition. Therefore, we hypothesize that catecholamines can modulate intermittent hypoxia induced TNF and further affect the developments of cardiovascular complications in OSA. In this project, we’ll use peripheral blood monocytes from healthy subjects and OSA patients as the target cells, which were serially treated with catecholamine  or b antagonists in both normoxic and hypoxic microenvironments, to achieve the following 3 objectives:

  1. . To examine the effect of catecholamines on the modulation of intermittent hypoxia induced TNF- in human monocytes from both healthy subjects and OSA patients
  2. . To map the signaling pathway of catecholamines regulating the intermittent hypoxia induced TNF- expression.
  3. . To explore the potential therapeutic effects of  or  agonists/antagonists on intermittent hypoxia induced TNF- expression

Study Type : Observational
Estimated Enrollment : 15 participants
Observational Model: Defined Population
Observational Model: Natural History
Time Perspective: Cross-Sectional
Time Perspective: Prospective
Study Start Date : September 2006




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy volunteer

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00498862


Contacts
Contact: Peilin Lee, M.D. +886-2-23562905 peilin1986@yahoo.com.tw

Locations
Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Peilin Lee, M.D.    +882-2-23562905    peilin1986@yahoo.com.tw   
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Peiln Lee, M.D. National Taiwan Univerisity Hospital
Principal Investigator: Peilin Lee, M.D. National Taiwan University Hospital

ClinicalTrials.gov Identifier: NCT00498862     History of Changes
Other Study ID Numbers: 9561709069
First Posted: July 10, 2007    Key Record Dates
Last Update Posted: July 10, 2007
Last Verified: September 2006