Endotoxemia, Inflammation, Innate Immune Response, Sepsis
Conditions
Brief summary
Excessive inflammation is associated with tissue damage caused by over-activation of the innate immune system. This can range from mild disease to extreme conditions, such as multiple organ dysfunction syndrome (MODS) and acute respiratory distress (ARDS). In marked contrast to adaptive immunity which is very sensitive to immune modulators such as steroids, the innate immune system cannot be sufficiently targeted by currently available anti-inflammatory drugs. The investigators hypothesize that pre-treatment with C1-esterase inhibitor in a human endotoxemia model can modulate the innate immune response. In this study, human endotoxemia will be used as a model for inflammation. Subjects will, prior to endotoxin administration, receive C1 esterase inhibitor or placebo. Blood will be sampled to determine the levels of markers of the innate immune response.
Interventions
intravenously
DRUGEndotoxin
intravenously
Sponsors
UMC Utrecht
Prothya Biosolutions
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male volunteers (18-35 years old)
Exclusion criteria
* Relevant medical history * Drug-, nicotine-abuses * Tendency towards fainting * Hyper- or hypotension * Use of any medication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Neutrophil phenotype and redistribution | 8 hrs after LPS administration |
Secondary
| Measure | Time frame |
|---|---|
| Cytokines and other markers of inflammation | 8 hrs after LPS administration |
| C1-inhibitor and complement concentration and activity | 8 hrs after LPS administration |
Countries
Netherlands
Outcome results
None listed