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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00246714
Other study ID # PP03
Secondary ID
Status Completed
Phase Phase 1
First received October 28, 2005
Last updated April 14, 2008
Start date October 2005
Est. completion date December 2007

Study information

Verified date April 2008
Source Radboud University
Contact n/a
Is FDA regulated No
Health authority Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Study type Interventional

Clinical Trial Summary

A number of diseases lead to a so called systemic inflammatory response syndrome (SIRS). This excessive response is self-destructive and leads to major complications of the initial disease: dysfunction of the microcirculation, systemic vasodilation, and increased capillary leakage and oedema. Animal studies have shown that pre-treatment with endotoxin (lipopolysaccharide or LPS) suppress the excessive immune response and when rechallenged, the animal survive a normally lethal dose of endotoxin.

Besides a diminished cytokine response, an increased production of leucocytes in the bone marrow and an increased phagocytosis after pre-treatment with endotoxin is seen. The combination of these factors: diminished systemic inflammatory response and increased cellular immunity makes that endotoxin tolerance is a useful tool for preventing the complications after an excessive inflammatory response.

Further, the presence of cross-tolerance has also been shown: Endotoxin tolerant mice survive more after induction of a normally lethal fungal infection. Endotoxin tolerance is also protective for ischemia/reperfusion injury in kidneys, heart and liver. Little data is known about endotoxin tolerance in human.

The purpose of this study is to induce a state of tolerance through 2 different administration schedules and monitor the effect of tolerance on pro- and anti-inflammatory cytokines, other inflammatory parameters and different proteins involved in the signalling pathway. The effects of tolerance on vascular reactivity will be determined. Finally, the effect of tolerance on ischemia-reperfusion injury will be investigated.


Description:

See protocol


Recruitment information / eligibility

Status Completed
Enrollment 16
Est. completion date December 2007
Est. primary completion date December 2007
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Male
Age group 18 Years to 35 Years
Eligibility Inclusion Criteria:

- Healthy male volunteers

Exclusion Criteria:

- drug-, nicotine-, alcohol abuses

- tendency towards fainting

- BMI < 18 kg/m2

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic


Related Conditions & MeSH terms


Intervention

Drug:
repeated injections of endotoxin during 5 days


Locations

Country Name City State
Netherlands Radboud University Nijmegen Medical Center Nijmegen Gelderland

Sponsors (1)

Lead Sponsor Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Primary inducing endotoxin tolerance 5 days No
Primary Hemodynamics 5 days No
Primary Markers of Inflammation 5 days No
Primary Cytokines 5 days No
Primary Mediators of Vascular reactivity 5 days No
Primary Sensitivity to norepinephrine 5 days No
Primary Endothelial-dependent vasorelaxation 5 days No
Primary Cross tolerance 6 days No
Primary Ischemia-reperfusion injury 6 days No
Primary Effects on tissue saturation (measured by NIRS) 24 hrs after LPS administration No
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