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

Sponsor
Radboud University Medical Center
Study ID
NCT06624436
Phase
PHASE4
Status
Recruiting
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Conditions

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

Eligibility Criteria

Sex
MALE
Age
18 Years - 35 Years
Healthy Volunteers
Accepted

Interventions

  • Dexamethasone — DRUG
    Dexamethasone 6mg in 10mL NaCl 0.9% i.v. bolus + 100mL NaCl 0.9% placebo infusion in 1 hour on the first LPS challenge.
  • Tocilizumab — DRUG
    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.
  • Anakinra — DRUG
    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.
  • Placebo — DRUG
    Bolus of 10mL NaCl 0.9% placebo + 100mL NaCl 0.9% placebo infusion in 1 hour on the first LPS challenge.
  • LPS — BIOLOGICAL
    This is a non-investigational product. It is used as challenge agent to achieve a controlled inflammatory state.

Study Details

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.

Key Dates

Start date
Oct 24, 2024
Status verified
Sep 2024
Primary completion
Sep 30, 2025
Completion
Dec 31, 2025

Study Design

Enrollment
52 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • 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.

Primary Outcome Measure

Between-group differences in plasma TNF concentrations upon the second LPS challenge [ Time Frame: 1 day (during second LPS challenge) ]

Central Contacts

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