Effect of Selective iNOS Inhibition During Human Endotoxemia

Phase 1

Completed

• Conditions: Endotoxemia

• Registration Number: NCT00184990
• Lead Sponsor: Radboud University Medical Center

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2005-01
• Primary Completion: 2005-09
• Study Completion: 2005-09
• Study First Submitted: 2005-09-12
• Study First Submitted QC: 2005-09-12
• Study First Posted: 2005-09-16
• Status Verified: 2008-04
• Last Update Submitted: 2008-04-14
• Last Update Posted: 2008-04-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

• Healthy volunteers

Exclusion Criteria

• tendency towards fainting
• alcohol abuse
• nicotine abuse
• drugs abuse

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Markers of Renal Injury	24 hrs after LPS administration
Inducible NO synthase expression	24 hrs after LPS administration
NO-metabolites	24 hrs after LPS administration
Mediators of Vascular reactivity	24 hrs after LPS administration
Sensitivity to norepinephrine	24 hrs after LPS administration
Endothelial-dependent vasorelaxation	24 hrs after LPS administration
Markers of Inflammation	24 hrs after LPS administration
Cytokines	24 hrs after LPS administration
Hemodynamics	24 hrs after LPS administration

Trial Locations

Locations (1)

Radboud University Nijmegen Medical Centre; 🇳🇱 Nijmegen, Gelderland, Netherlands