Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06624436
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-20
Brief Title:
Immunomodulatory Effects of Dexamethasone Tocilizumab and Anakinra During Experimental Human Endotoxemia
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Immunomodulatory Effects of Dexamethasone Tocilizumab and Anakinra During Experimental Human Endotoxemia
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DEDICATE-LPS
Brief Summary:
The goal of this clinical trial is to investigate the immunomodulatory effects of the drugs dexamethasone tocilizumab and anakinra in healthy male subjects aged 18 to 35 undergoing experimental endotoxemia The main questions it aims to answer are
What are the effects of these drugs on the development of immunoparalysis in a repeated human endotoxemia model
What is the extent of the neuroinflammatory response and how do these drugs affect neuroinflammation in a repeated human endotoxemia model
Researchers will compare these drugs to a placebo a look-alike substance that contains no drug
Participants will visit the Intensive Care research department on two or five occasions screening included
The intervention group will receive an LPS challenge twice with a week in between Before the first LPS challenge one of the described drugs will be administered Blood saliva and tear fluid will be collected regularly during the LPS challenge Cerebrospinal fluid will also be collected through a catheter in the spinal cord
The control group will not receive an LPS challenge or drug administration and will have only one study day During this day blood saliva tear fluid and cerebrospinal fluid will be collected as regularly as during the LPS challenge of the intervention group
During an LPS challenge the investigators mimic blood poisoning by giving an endotoxin also called LPS This is a small part of the cell wall of a bacteria This will cause transient flu-like symptoms for 3-4 hours
What are the effects of these drugs on the development of immunoparalysis in a repeated human endotoxemia model
What is the extent of the neuroinflammatory response and how do these drugs affect neuroinflammation in a repeated human endotoxemia model
Researchers will compare these drugs to a placebo a look-alike substance that contains no drug
Participants will visit the Intensive Care research department on two or five occasions screening included
The intervention group will receive an LPS challenge twice with a week in between Before the first LPS challenge one of the described drugs will be administered Blood saliva and tear fluid will be collected regularly during the LPS challenge Cerebrospinal fluid will also be collected through a catheter in the spinal cord
The control group will not receive an LPS challenge or drug administration and will have only one study day During this day blood saliva tear fluid and cerebrospinal fluid will be collected as regularly as during the LPS challenge of the intervention group
During an LPS challenge the investigators mimic blood poisoning by giving an endotoxin also called LPS This is a small part of the cell wall of a bacteria This will cause transient flu-like symptoms for 3-4 hours
Detailed Description:
The experimental human endotoxemia model is a controlled standardized and safe model of systemic sepsis-like inflammation induced by bacterial lipopolysaccharide LPS in healthy volunteers This model captures many hallmarks of both the hyperinflammatory phenotype observed following a first LPS challenge and the immunoparalytic phenotype observed following a second LPS challenge one week later of sepsis
In this study the investigators aim to determine the effects of dexamethasone tocilizumab and anakinra within the repeated experimental human endotoxemia model on the development of immunoparalysis reflected by between-group differences in plasma TNF and other cytokine concentrations upon the second LPS challenge The investigators will also profile inflammatory parameters in cerebrospinal fluid CSF reflected by within- and between-group differences in CSF TNF and other cytokine concentrations following the first LPS challenge to gain insights in inflammatory responses of the central nervous system
Anti-inflammatory drugs may help reduce sepsis-induced immunoparalysis and somewhat counterintuitively improve immune responses later by dampening the initial hyperinflammation Pro-inflammatory cytokines such as TNF are key in triggering this immunosuppression Reducing early hyperinflammation could also prevent postoperative immune suppression lowering the risk of infections Drugs like dexamethasone tocilizumab and anakinra may affect neuroinflammation depending on their ability to cross the blood-brain barrier BBB
Furthermore the investigators will explore whether cytokine profiles in saliva and tear fluid can be used as a proxy for circulating cytokine responses Saliva and tear fluid cytokines may serve as non-invasive alternatives to blood measurements especially for vulnerable populations though more research is needed to validate their reliability
Comprehensive assessment of cellular components and cytokine dynamics in blood CSF saliva and tear fluid will be conducted using RNA sequencing providing insights into cellular and molecular mechanisms during endotoxemia and drug effects This research will help identify new drug targets and better understand the immunomodulatory effects of dexamethasone tocilizumab and anakinra on inflammation and immunosuppression
In this study the investigators aim to determine the effects of dexamethasone tocilizumab and anakinra within the repeated experimental human endotoxemia model on the development of immunoparalysis reflected by between-group differences in plasma TNF and other cytokine concentrations upon the second LPS challenge The investigators will also profile inflammatory parameters in cerebrospinal fluid CSF reflected by within- and between-group differences in CSF TNF and other cytokine concentrations following the first LPS challenge to gain insights in inflammatory responses of the central nervous system
Anti-inflammatory drugs may help reduce sepsis-induced immunoparalysis and somewhat counterintuitively improve immune responses later by dampening the initial hyperinflammation Pro-inflammatory cytokines such as TNF are key in triggering this immunosuppression Reducing early hyperinflammation could also prevent postoperative immune suppression lowering the risk of infections Drugs like dexamethasone tocilizumab and anakinra may affect neuroinflammation depending on their ability to cross the blood-brain barrier BBB
Furthermore the investigators will explore whether cytokine profiles in saliva and tear fluid can be used as a proxy for circulating cytokine responses Saliva and tear fluid cytokines may serve as non-invasive alternatives to blood measurements especially for vulnerable populations though more research is needed to validate their reliability
Comprehensive assessment of cellular components and cytokine dynamics in blood CSF saliva and tear fluid will be conducted using RNA sequencing providing insights into cellular and molecular mechanisms during endotoxemia and drug effects This research will help identify new drug targets and better understand the immunomodulatory effects of dexamethasone tocilizumab and anakinra on inflammation and immunosuppression
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