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Effect of Selective iNOS Inhibition During Human Endotoxemia

This study has been completed.
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00184990
First received: September 12, 2005
Last updated: April 14, 2008
Last verified: April 2008

September 12, 2005
April 14, 2008
January 2005
September 2005   (final data collection date for primary outcome measure)
  • Hemodynamics [ Time Frame: 24 hrs after LPS administration ]
  • Markers of Inflammation [ Time Frame: 24 hrs after LPS administration ]
  • Cytokines [ Time Frame: 24 hrs after LPS administration ]
  • Markers of Renal Injury [ Time Frame: 24 hrs after LPS administration ]
  • Inducible NO synthase expression [ Time Frame: 24 hrs after LPS administration ]
  • NO-metabolites [ Time Frame: 24 hrs after LPS administration ]
  • Mediators of Vascular reactivity [ Time Frame: 24 hrs after LPS administration ]
  • Sensitivity to norepinephrine [ Time Frame: 24 hrs after LPS administration ]
  • Endothelial-dependent vasorelaxation [ Time Frame: 24 hrs after LPS administration ]
  • Hemodynamics
  • Markers of Inflammation
  • Cytokines
  • Markers of Renal Injury
  • Inducible NO synthase expression
  • NO-metabolites
  • Mediators of Vascular reactivity
  • Sensitivity to norepinephrine
  • Endothelial-dependent vasorelaxation
Complete list of historical versions of study NCT00184990 on ClinicalTrials.gov Archive Site
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Effect of Selective iNOS Inhibition During Human Endotoxemia
Effect of Selective iNOS Inhibition During Human Endotoxemia

Sepsis or endotoxemia is manifested by hypotension, resistance to vasopressors, myocardial depression,and altered organ blood flow distribution. The mechanisms underlying the cardiovascular dysfunction during sepsis are complex; however, they are partially mediated by an uncontrolled production of NO by inducible NO synthase (iNOS).Control subjects received 2 ng/kg E. coli endotoxin, whereas the active intervention group received endotoxin in the presence of selective iNOS-inhibitor aminoguanidine. Hemodynamics, vascular responses to norepinephrine, acetylcholine and sodium nitroprusside, as well as circulating cytokines and other mediators of inflammation were measured. We tested the hypothesis that inhibition of NO-synthesis prevented the LPS-mediated insensitivity to noradrenalin and endothelial-dependent vasorelaxation. Furthermore, we tested whether NO participates in occurrence of the endotoxin tolerance in humans by using the iNOS inhibitor aminoguanidine on healthy volunteers with endotoxemia. At 0; 2 and 4 hours after the LPS challenge whole blood was stimulated with five TLR agonists in vitro and pro- and anti-inflammatory cytokines were measured.

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Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Endotoxemia
  • Drug: Aminoguanidine
  • Drug: endotoxin
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
7
September 2005
September 2005   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Healthy volunteers

Exclusion Criteria:

  • tendency towards fainting
  • alcohol abuse
  • nicotine abuse
  • drugs abuse
Both
18 Years to 35 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT00184990
PP01
No
Not Provided
Radboud University
Not Provided
Principal Investigator: Peter Pickkers, PhD Radboud University
Radboud University
April 2008

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