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OpenTrials
Completed

NCT Number: NCT00184990

Effect of Selective iNOS Inhibition During Human Endotoxemia

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.

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Key information

Conditions

Endotoxemia Bacteremia Infections Inflammation Pathologic Processes Pathological Conditions, Signs and Symptoms Sepsis Systemic Inflammatory Response Syndrome Toxemia

Age range

18 year–35 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, 6500HB, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy volunteers

Exclusion criteria

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

Treatment and study plan

Aminoguanidine

Drug

Endotoxin

Drug

Primary outcomes

  1. Hemodynamics

    Time frame: 24 hrs after LPS administration

  2. Markers of Inflammation

    Time frame: 24 hrs after LPS administration

  3. Cytokines

    Time frame: 24 hrs after LPS administration

  4. Markers of Renal Injury

    Time frame: 24 hrs after LPS administration

  5. Inducible NO synthase expression

    Time frame: 24 hrs after LPS administration

  6. NO-metabolites

    Time frame: 24 hrs after LPS administration

  7. Mediators of Vascular reactivity

    Time frame: 24 hrs after LPS administration

  8. Sensitivity to norepinephrine

    Time frame: 24 hrs after LPS administration

  9. Endothelial-dependent vasorelaxation

    Time frame: 24 hrs after LPS administration

Sponsors and collaborators

Lead sponsor

Radboud University Medical Center

Other

Registry information

Important dates

Study start
2005
Primary completion
2005
Study completion
2005
First posted
Sep 16, 2005
Registry last updated
Apr 15, 2008

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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