NCT00185003

Brief Summary

Background: Activation of NO-synthase and vascular potassium (K) channels may play a role in the sepsis-induced attenuated sensitivity to norepinephrine. We examined whether various K channel blockers and NO-synthase inhibition could restore norepinephrine sensitivity during experimental human endotoxemia.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
36

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jan 2003

Typical duration for phase_1

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2003

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2005

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2005

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

September 13, 2005

Completed
3 days until next milestone

First Posted

Study publicly available on registry

September 16, 2005

Completed
Last Updated

October 17, 2008

Status Verified

April 1, 2008

Enrollment Period

2.4 years

First QC Date

September 13, 2005

Last Update Submit

October 16, 2008

Conditions

Endotoxemia

Keywords

Endotoxemiavascular potassium channelscytokinenorepinephrineregional blood flow,inflammation,ion channels,nitric oxide synthase,pharmacology.

Outcome Measures

Primary Outcomes (8)

  • Hemodynamics

    24 hrs after LPS administration

  • Markers of Inflammation

    24 hrs after LPS administration

  • Cytokines

    24 hrs after LPS administration

  • Markers of Renal Injury

    24 hrs after LPS administration

  • Inducible NO synthase expression

    24 hrs after LPS administration

  • NO-metabolites

    24 hrs after LPS administration

  • Mediators of Vascular reactivity

    24 hrs after LPS administration

  • Sensitivity to norepinephrine

    24 hrs after LPS administration

Interventions

endotoxinDRUG
Potassium channel blockers: TEA, Quinin, TolbutamideDRUG
L-NMMADRUG

Eligibility Criteria

Age18 Years - 35 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • healthy volunteers

You may not qualify if:

  • drug, alcohol, nicotine abuse

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (1)

  • Pickkers P, Dorresteijn MJ, Bouw MP, van der Hoeven JG, Smits P. In vivo evidence for nitric oxide-mediated calcium-activated potassium-channel activation during human endotoxemia. Circulation. 2006 Aug 1;114(5):414-21. doi: 10.1161/CIRCULATIONAHA.105.590232. Epub 2006 Jul 24.

    PMID: 16864730RESULT

MeSH Terms

Conditions

EndotoxemiaInflammation

Interventions

EndotoxinsTolbutamideomega-N-Methylarginine

Condition Hierarchy (Ancestors)

BacteremiaSepsisInfectionsToxemiaSystemic Inflammatory Response SyndromePathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bacterial ToxinsToxins, BiologicalBiological FactorsBenzenesulfonamidesSulfonamidesAmidesOrganic ChemicalsSulfonylurea CompoundsUreaBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSulfonesSulfur CompoundsArginineAmino Acids, BasicAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, DiaminoAmino Acids, Essential

Study Officials

  • Peter Pickkers, MD, PhD

    Radboud University Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

September 13, 2005

First Posted

September 16, 2005

Study Start

January 1, 2003

Primary Completion

June 1, 2005

Study Completion

June 1, 2005

Last Updated

October 17, 2008

Record last verified: 2008-04