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Effect of Selective iNOS Inhibition During Human Endotoxemia

NCT00184990 · Status: COMPLETED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 7

Last updated 2008-04-15

No results posted yet for this study

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

DRUG

Aminoguanidine

DRUG

endotoxin

Sponsors & Collaborators

  • Radboud University Medical Center

    lead OTHER

Principal Investigators

  • Peter Pickkers, PhD · Radboud University Medical Center

Study Design

Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
35 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2005-01-31
Primary Completion
2005-09-30
Completion
2005-09-30

Countries

  • Netherlands

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00184990 on ClinicalTrials.gov