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Effect of Selective iNOS Inhibition During Human Endotoxemia

R

Radboud University Medical Center

Status and phase

Completed
Phase 1

Conditions

Endotoxemia

Treatments

Drug: Aminoguanidine
Drug: endotoxin

Study type

Interventional

Funder types

Other

Identifiers

Details and patient eligibility

About

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.

Enrollment

7 patients

Sex

All

Ages

18 to 35 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

  • Healthy volunteers

Exclusion criteria

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

Trial design

Primary purpose

Prevention

Allocation

Non-Randomized

Interventional model

Single Group Assignment

Masking

None (Open label)

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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