Ignite Creation Date:
2024-05-05 @ 11:37 PM
Last Modification Date:
2024-10-26 @ 10:36 AM
Study NCT ID:
NCT01374711
Status:
COMPLETED
Last Update Posted:
2013-06-27
First Post:
2011-05-19
Brief Title:
The Effects of Immunostimulation With GM-CSF or IFN-y on Immunoparalysis Following Human Endotoxemia
Sponsor:
Radboud University Medical Center
Organization:
Radboud University Medical Center
Study Overview
Official Title:
The Effects of Immunostimulation With GM-CSF or IFN-y on Immunoparalysis Following Human Endotoxemia A Parallel Randomized Double-blind Placebo-controlled Study
Status:
COMPLETED
Status Verified Date:
2013-06
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:
The human body knows a biphasic immunological reaction to sepsis First the pro-inflammatory reaction takes place marked by the release of pro-inflammatory cytokines like TNF-α as a reaction to the bacterial toxins Secondly the counter regulatory anti-inflammatory reaction arises This phase is acting as negative feedback on the inflammation by inhibition of the pro-inflammatory cytokines This is called immunoparalysis a pronounced immunosuppressive state which renders patients vulnerable to opportunistic infections Most of the septic patients survive the initial pro-inflammatory phase but die during this second stageResearch in the past has shown that immunostimulatory therapy with GM-CSF or IFN-γ has promising effects on the pro-inflammatory reaction during immunoparalysis ex vivo Both drugs are known for their immunostimulatory effects Recent pilot studies have showed in septic patients that long-lasting monocyte deactivation in sepsis ex vivo can be reversed by these two immunostimulants However the mechanism and extent of immunoparalysis recovery may be different between the two compounds Previously it has been shown that human endotoxemia induced by LPS leads to marked immunosuppression in healthy individuals characterized by a transient refractory state to a subsequent LPS challenge endotoxin tolerance Consequently human endotoxemia can serve as a standardized controlled model for sepsis-induced immunoparalysis Until now all studies have focused on the ex vivo tolerance However we have recently proved that the ex vivo condition is not completely representative for the in vivo situation Ex vivo leukocyte tolerance to LPS resolves within one day while the in vivo immunoparalysis persists for two weeks In this project we will investigate the effects of both GM-CSF and IFN-γ in a parallel double-blind placebo controlled randomized manner on the immunoparalysis following human endotoxemia both in-vitro and in vivo As a result we hope to get more insight in the pathophysiology of sepsis-induced immunoparalysis and thereby develop new immunostimulatory therapies that improve patient outcome
Detailed Description:
None
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