Immunomodulatory Effects of Dexamethasone, Tocilizumab and Anakinra During Experimental Human Endotoxemia

Status: Recruiting
Location: See location...
Intervention Type: Biological, Drug
Study Type: Interventional
Study Phase: Phase 4
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.

Eligibility
Participation Requirements
Sex: Male
Minimum Age: 18
Maximum Age: 35
Healthy Volunteers: t
View:

• Male subjects aged ≥18 and ≤35 years

• Body mass index (BMI) ≥18 and ≤30 kg/m2

• Healthy (as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram and routine clinical laboratory parameters)

• Able to comprehend and sign the Information letter and Informed Consent (IC) prior to enrolment in the study.

Locations
Other Locations
Netherlands
Intensive Care Medicine, Radboud University Nijmegen Medical Centre
RECRUITING
Nijmegen
Contact Information
Primary
Nicole Waalders, MD
nicole.waalders@radboudumc.nl
+31243668420
Backup
Matthijs Kox, PhD
matthijs.kox@radboudumc.nl
+31243653881
Time Frame
Start Date: 2024-10-24
Estimated Completion Date: 2025-12
Participants
Target number of participants: 52
Treatments
Active_comparator: Group 1: dexamethasone
This arm (n = 12) of healthy male volunteers will have two LPS challenges (day 0 and day 7) and will receive dexamethasone infusion in 1 hour on the first LPS challenge.
Active_comparator: Group 2: Tocilizumab
This arm (n = 12) of healthy male volunteers will have two LPS challenges (day 0 and day 7) and will receive Tocilizumab infusion in 1 hour on the first LPS challenge.
Active_comparator: Group 3: Anakinra
This arm (n = 12) of healthy male volunteers will have two LPS challenges (day 0 and day 7) and will receive Anakinra infusion in 1 hour on the first LPS challenge.
Placebo_comparator: Group 4: Placebo
This arm (n = 12) of healthy male volunteers will have two LPS challenges (day 0 and day 7) and will receive a placebo infusion in 1 hour on the first LPS challenge.
No_intervention: Group 5: Control
This arm (n = 4) of healthy male volunteers won't receive an LPS challenge or any of the study treatments. This group will be used to familiarise the study team with the study procedures and to establish the effect of placement of an intrathecal catheter on systemic and neuroinflammation.
Related Therapeutic Areas
Sponsors
Leads: Radboud University Medical Center

This content was sourced from clinicaltrials.gov