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

Launched by RADBOUD UNIVERSITY MEDICAL CENTER · Sep 30, 2024

Keywords

ClinConnect Summary

This clinical trial is studying the effects of three different medications—dexamethasone, tocilizumab, and anakinra—on the immune system during a controlled experiment that mimics a condition called endotoxemia, which is similar to blood poisoning. The main goal is to understand how these drugs might help reduce immune system suppression and inflammation in healthy young men aged 18 to 35. Some participants will receive the medications along with a substance that causes temporary flu-like symptoms, while others will not receive any drugs and will serve as a control group.

To participate, men must be between 18 and 35 years old, in good health, and not taking any medications that could interfere with the study. Participants will have several visits to the research department, where they will undergo tests and provide samples of blood and other fluids. It’s important to know that this study is still recruiting participants, and those interested should be aware of the detailed eligibility criteria, including avoiding certain health conditions and medications.

Gender

MALE

Eligibility criteria

• 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