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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified September 2006 by National Taiwan University Hospital.
Recruitment status was:  Recruiting
Sponsor:
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00498862
First received: July 8, 2007
Last updated: July 9, 2007
Last verified: September 2006
July 8, 2007
July 9, 2007
September 2006
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No Changes Posted
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Catecholamines Can Attenuate Intermittent Hypoxia-Induced Expression of TNF in Human Monocytes
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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

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
Observational
Observational Model: Defined Population
Observational Model: Natural History
Time Perspective: Cross-Sectional
Time Perspective: Prospective
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Healthy
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Unknown status
15
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Inclusion Criteria:

  • Healthy volunteer
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Yes
Contact information is only displayed when the study is recruiting subjects
Taiwan
 
 
NCT00498862
9561709069
Yes
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National Taiwan University Hospital
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Principal Investigator: Peiln Lee, M.D. National Taiwan Univerisity Hospital
Principal Investigator: Peilin Lee, M.D. National Taiwan University Hospital
National Taiwan University Hospital
September 2006

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP