Pathophysiology and Clinical Relevance of Endotoxin Tolerance in Humans
1 other identifier
interventional
16
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Oct 2005
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2005
CompletedFirst Submitted
Initial submission to the registry
October 28, 2005
CompletedFirst Posted
Study publicly available on registry
October 31, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2007
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2007
CompletedApril 15, 2008
April 1, 2008
2.2 years
October 28, 2005
April 14, 2008
Conditions
Keywords
Outcome Measures
Primary Outcomes (10)
inducing endotoxin tolerance
5 days
Hemodynamics
5 days
Markers of Inflammation
5 days
Cytokines
5 days
Mediators of Vascular reactivity
5 days
Sensitivity to norepinephrine
5 days
Endothelial-dependent vasorelaxation
5 days
Cross tolerance
6 days
Ischemia-reperfusion injury
6 days
Effects on tissue saturation (measured by NIRS)
24 hrs after LPS administration
Interventions
Eligibility Criteria
You may qualify if:
- Healthy male volunteers
You may not qualify if:
- drug-, nicotine-, alcohol abuses
- tendency towards fainting
- BMI \< 18 kg/m2
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Radboud University Nijmegen Medical Center
Nijmegen, Gelderland, 6500HB, Netherlands
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Peter Pickkers, MD PhD
Radboud University Nijmegen Medical Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- DIAGNOSTIC
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
October 28, 2005
First Posted
October 31, 2005
Study Start
October 1, 2005
Primary Completion
December 1, 2007
Study Completion
December 1, 2007
Last Updated
April 15, 2008
Record last verified: 2008-04