Blockade of Vascular Potassium Channels During Human Endotoxemia - Full Text View

Sponsors and Collaborators:	Radboud University ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by:	Radboud University
ClinicalTrials.gov Identifier:	NCT00185003

Purpose

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.

Condition	Intervention	Phase
Endotoxemia	Drug: endotoxin Drug: Potassium channel blockers: TEA, Quinin, Tolbutamide Drug: L-NMMA	Phase I

Drug Information available for: Nitric oxide Potassium chloride Tolbutamide Norepinephrine Norepinephrine bitartrate omega-N-Methylarginine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Pharmacokinetics/Dynamics Study
Official Title:	Blockade of Vascular Potassium Channels During Human Endotoxemia

Further study details as provided by Radboud University:

Primary Outcome Measures:

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 ]
Mediators of Vascular reactivity [ Time Frame: 24 hrs after LPS administration ]
Sensitivity to norepinephrine [ Time Frame: 24 hrs after LPS administration ]

Enrollment:	36
Study Start Date:	January 2003
Study Completion Date:	June 2005
Primary Completion Date:	June 2005 (Final data collection date for primary outcome measure)

Eligibility

Ages Eligible for Study:	18 Years to 35 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

healthy volunteers

Exclusion Criteria:

drug, alcohol, nicotine abuse

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00185003

Sponsors and Collaborators

Radboud University

ZonMw: The Netherlands Organisation for Health Research and Development

Investigators

Principal Investigator:

Peter Pickkers, MD, PhD

Radboud University

More Information

Publications of Results:

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. Epub 2006 Jul 24.

Study ID Numbers:	PP02, ZONMW grant 907-00-056
Study First Received:	September 13, 2005
Last Updated:	October 16, 2008
ClinicalTrials.gov Identifier:	NCT00185003
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:

Endotoxemia
vascular potassium channels
cytokine
norepinephrine
regional blood flow,

inflammation,
ion channels,
nitric oxide synthase,
pharmacology.

Study placed in the following topic categories:

Nitric Oxide
Systemic Inflammatory Response Syndrome
Sepsis
Omega-N-Methylarginine
Norepinephrine

Bacteremia
Endotoxemia
Tolbutamide
Toxemia
Inflammation

Additional relevant MeSH terms:

Hypoglycemic Agents
Pathologic Processes
Physiological Effects of Drugs
Infection
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009