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

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.

Conditions

• Sepsis
• Neuroinflammatory Response
• Immunosuppresion
• Endotoxemia
• Anakinra
• Dexamethasone
• Tocilizumab

Interventions

DRUG

Dexamethasone

Dexamethasone 6mg in 10mL NaCl 0.9% i.v. bolus + 100mL NaCl 0.9% placebo infusion in 1 hour on the first LPS challenge.

DRUG

Tocilizumab

Tocilizumab 600mg in 100mL NaCl 0.9% i.v. in 1 hour + a bolus of 10mL NaCl 0.9% placebo infusion on the first LPS challenge.

DRUG

Anakinra

Anakinra 200mg in 100mL NaCl 0.9% i.v. in 1 hour + a bolus of 10mL NaCl 0.9% placebo infusion on the first LPS challenge.

DRUG

Placebo

Bolus of 10mL NaCl 0.9% placebo + 100mL NaCl 0.9% placebo infusion in 1 hour on the first LPS challenge.

BIOLOGICAL

LPS

This is a non-investigational product. It is used as challenge agent to achieve a controlled inflammatory state.

Sponsors & Collaborators

• Radboud University Medical Center

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

35 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-10-24

Primary Completion

2025-09-30

Completion

2025-12-31

FDA Drug

Yes

Countries

• Netherlands

Study Locations