Pathophysiology and Clinical Relevance of Endotoxin Tolerance in Humans

NCT ID: NCT00246714

Last Updated: 2008-04-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-10-31

Study Completion Date

2007-12-31

Brief Summary

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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.

Detailed Description

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See protocol

Conditions

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Endotoxemia

Keywords

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endotoxin tolerance humans cross-tolerance pro and anti-inflammatory cytokines

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Interventions

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repeated injections of endotoxin during 5 days

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Healthy male volunteers

Exclusion Criteria

* drug-, nicotine-, alcohol abuses
* tendency towards fainting
* BMI \< 18 kg/m2
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Radboud University Medical Centre

Principal Investigators

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Peter Pickkers, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Nijmegen Medical Center

Locations

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Radboud University Nijmegen Medical Center

Nijmegen, Gelderland, Netherlands

Site Status

Countries

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Netherlands

Other Identifiers

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PP03

Identifier Type: -

Identifier Source: org_study_id