Ignite Creation Date:
2024-05-05 @ 12:07 PM
Last Modification Date:
2024-10-26 @ 9:20 AM
Study NCT ID:
NCT00246714
Status:
COMPLETED
Last Update Posted:
2008-04-15
First Post:
2005-10-28
Brief Title:
Pathophysiology and Clinical Relevance of Endotoxin Tolerance in Humans
Sponsor:
Radboud University Medical Center
Organization:
Radboud University Medical Center
Study Overview
Official Title:
Pathophysiology and Clinical Relevance of Endotoxin Tolerance in Humans
Status:
COMPLETED
Status Verified Date:
2008-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 ischemiareperfusion 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
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 ischemiareperfusion 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:
See protocol
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None