Effect of Selective iNOS Inhibition During Human Endotoxemia

NCT ID: NCT00184990

Last Updated: 2008-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2005-09-30

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.

Conditions

Endotoxemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Interventions

Aminoguanidine

Intervention Type: DRUG

endotoxin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy volunteers

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Principal Investigators

Peter Pickkers, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, Netherlands

Countries

Netherlands

Other Identifiers

PP01

Identifier Type: -

Identifier Source: org_study_id