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RECRUITING

NCT06624436

PHASE4

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

Sponsor: Radboud University Medical Center

View on ClinicalTrials.gov

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.

Key Details

Gender

MALE

Age Range

18 Years - 35 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2024-10-24

Completion Date

2025-12

Last Updated

2025-04-04

Healthy Volunteers

Yes

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.

Inclusion Criteria: * 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. Exclusion Criteria: * Use of any prescription medication or over-the-counter non-steroidal anti-inflammatory drugs * Known anaphylaxis or hypersensitivity to any (non-)investigational products or their excipients * History of chronic headache or previous post-dural puncture headache (PDPH) * History or signs of severe atopic syndrome (asthma, rhinitis with medication and/or eczema) * History of any disease associated with immune deficiency * History of cancer in the last 5 years (excluding localised skin cancer or carcinoma in situ) * History or signs of haematological disease * History or signs of thromboembolic disorders * History of peptic / gastric ulcer disease * History of psychiatric disorders * Thrombocytopenia (\<150\*109/mL) or anaemia (\<8.0 mmol/L) * History, signs or symptoms of cardiovascular disease, in particular: * Prone to vagal collapse * History of atrial or ventricular arrhythmia * Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrio-ventricular block or a complete left bundle branch block * Hypertension (defined as RR systolic \> 160 or RR diastolic \> 90 mmHg) * Hypotension (defined as RR systolic \< 100 or RR diastolic \< 50 mmHg) * Renal impairment (defined as plasma creatinine \>120 μmol/L) * Liver enzyme abnormalities (above 2x the upper limit of normal) * Signs of infection (CRP \> 20 mg/L, white blood cells \> 12x109/L or * lt; 4x109/L) * Clinically significant acute illness, including infections or trauma, within 1 month prior to the first LPS challenge * Previous (participation in a study with) endotoxin (LPS) administration * Participation in an experimental intervention or drug trial within 3 months prior to the first LPS challenge * Any vaccination or blood donation within 1 month prior to the first LPS challenge * Recent hospital admission or surgery with general anaesthesia within 3 months prior to the first LPS challenge * Use of recreational drugs within 2 weeks prior to the first LPS challenge * Suspected of not being able to comply with the trial protocol * Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study

Locations (1)

Intensive Care Medicine, Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, Netherlands

Clinical Research Directory

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

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (1)