NCT00184990

Effect of Selective iNOS Inhibition During Human Endotoxemia

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 7 (actual)
• Sponsor: Radboud University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

Summary

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.

Conditions

• Endotoxemia

Interventions

Type	Name	Description
DRUG	Aminoguanidine
DRUG	endotoxin

Timeline

• Start date: 2005-01-01
• Primary completion: 2005-09-01
• Completion: 2005-09-01
• First posted: 2005-09-16
• Last updated: 2008-04-15

Locations

1 site across 1 country: Netherlands