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Sponsored by: |
Radboud University |
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Information provided by: | Radboud University |
ClinicalTrials.gov Identifier: | NCT00184990 |
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.
Condition | Intervention | Phase |
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Endotoxemia |
Drug: Aminoguanidine Drug: endotoxin |
Phase I |
Study Type: | Interventional |
Study Design: | Prevention, Non-Randomized, Open Label, Active Control, Single Group Assignment, Pharmacokinetics/Dynamics Study |
Official Title: | Effect of Selective iNOS Inhibition During Human Endotoxemia |
Enrollment: | 7 |
Study Start Date: | January 2005 |
Study Completion Date: | September 2005 |
Primary Completion Date: | September 2005 (Final data collection date for primary outcome measure) |
Ages Eligible for Study: | 18 Years to 35 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Netherlands, Gelderland | |
Radboud University Nijmegen Medical Centre | |
Nijmegen, Gelderland, Netherlands, 6500HB |
Principal Investigator: | Peter Pickkers, PhD | Radboud University |
Study ID Numbers: | PP01 |
Study First Received: | September 12, 2005 |
Last Updated: | April 14, 2008 |
ClinicalTrials.gov Identifier: | NCT00184990 |
Health Authority: | Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
Endotoxemia Aminoguanidine |
Systemic Inflammatory Response Syndrome Sepsis Bacteremia Endotoxemia |
Pimagedine Toxemia Inflammation |
Pathologic Processes Molecular Mechanisms of Pharmacological Action Enzyme Inhibitors Infection Pharmacologic Actions |