NCT00184990

Effect of Selective iNOS Inhibition During Human Endotoxemia

Completed Phase 1 Last updated 14 April 2008

What this trial tests

Phase 1 trial testing Aminoguanidine in Endotoxemia in 7 participants. Completed in 1 September 2005.

Timeline

1 January 2005

Primary endpoint
1 September 2005

1 September 2005

Quick facts

Lead sponsor	Radboud University Medical Center
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	prevention
Enrollment	7
Start date	1 January 2005
Primary completion	1 September 2005
Estimated completion	1 September 2005
Sites	1 location across Netherlands

Drugs / interventions tested

• Aminoguanidine — full drug profile →
• endotoxin — full drug profile →

Conditions studied

• Endotoxemia — all drugs for Endotoxemia →

Sponsor

Radboud University Medical Center

Who can join

Adults 18 to 35, any sex, with Endotoxemia. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Hemodynamics
  Time frame: 24 hrs after LPS administration
• Markers of Inflammation
  Time frame: 24 hrs after LPS administration
• Cytokines
  Time frame: 24 hrs after LPS administration
• Markers of Renal Injury
  Time frame: 24 hrs after LPS administration
• Inducible NO synthase expression
  Time frame: 24 hrs after LPS administration
• NO-metabolites
  Time frame: 24 hrs after LPS administration

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Recent clinical trends in Toll-like receptor targeting therapeutics.
   Anwar MA, Shah M, Kim J, Choi S. · · 2019 · cited 209× · PMID 30450666 · DOI 10.1002/med.21553
2. Pattern recognition receptors: function, regulation and therapeutic potential.
   Chen R, Zou J, Chen J, Zhong X, et al · · 2025 · cited 53× · PMID 40640149 · DOI 10.1038/s41392-025-02264-1