Effect of Selective iNOS Inhibition During Human Endotoxemia

Endotoxemia Clinical Trial

Official title:

Effect of Selective iNOS Inhibition During Human Endotoxemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00184990
• Other study ID #: PP01
• Status: Completed
• Phase: Phase 1
• First received: September 12, 2005
• Last updated: April 14, 2008
• Start date: January 2005
• Est. completion date: September 2005

Study information

• Verified date: April 2008
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: September 2005
• Est. primary completion date: September 2005
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Healthy volunteers

Exclusion Criteria:

• tendency towards fainting

• alcohol abuse

• nicotine abuse

• drugs abuse

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Endotoxemia

Intervention

Drug:
• Aminoguanidine

• endotoxin

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hemodynamics		24 hrs after LPS administration
Primary	Markers of Inflammation		24 hrs after LPS administration
Primary	Cytokines		24 hrs after LPS administration
Primary	Markers of Renal Injury		24 hrs after LPS administration
Primary	Inducible NO synthase expression		24 hrs after LPS administration
Primary	NO-metabolites		24 hrs after LPS administration
Primary	Mediators of Vascular reactivity		24 hrs after LPS administration
Primary	Sensitivity to norepinephrine		24 hrs after LPS administration
Primary	Endothelial-dependent vasorelaxation		24 hrs after LPS administration