NCT00184990

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
7

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jan 2005

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2005

Completed
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2005

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2005

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

September 12, 2005

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 16, 2005

Completed
Last Updated

April 15, 2008

Status Verified

April 1, 2008

Enrollment Period

8 months

First QC Date

September 12, 2005

Last Update Submit

April 14, 2008

Conditions

Endotoxemia

Keywords

EndotoxemiaAminoguanidine

Outcome Measures

Primary Outcomes (9)

  • Hemodynamics

    24 hrs after LPS administration

  • Markers of Inflammation

    24 hrs after LPS administration

  • Cytokines

    24 hrs after LPS administration

  • 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

Interventions

AminoguanidineDRUG
endotoxinDRUG

Eligibility Criteria

Age18 Years - 35 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy volunteers

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, 6500HB, Netherlands

Location

MeSH Terms

Conditions

Endotoxemia

Interventions

pimagedineEndotoxins

Condition Hierarchy (Ancestors)

BacteremiaSepsisInfectionsToxemiaSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bacterial ToxinsToxins, BiologicalBiological Factors

Study Officials

  • Peter Pickkers, PhD

    Radboud University Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER

Study Record Dates

First Submitted

September 12, 2005

First Posted

September 16, 2005

Study Start

January 1, 2005

Primary Completion

September 1, 2005

Study Completion

September 1, 2005

Last Updated

April 15, 2008

Record last verified: 2008-04

Locations

NL(1)