In Vivo Effects of C1-esterase Inhibitor on the Innate Immune Response During Human Endotoxemia - VECTOR II

Study Overview
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Brief Summary
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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.

Official Title
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In Vivo Effects of C1-esterase Inhibitor on the Innate Immune Response During Human Endotoxemia - A Randomized Controlled Pilot Study

Conditions
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Innate Immune Response, Endotoxemia, Inflammation, Sepsis

Intervention / Treatment
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* Drug: C1-esterase inhibitor
* Drug: Endotoxin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: C1-esterase inhibitor<br>C1-esterase inhibitor 100 U/kg infusion followed by administration of Endotoxin 2ng/kg | Drug: C1-esterase inhibitor<br>* intravenously<br>* Other names: Cetor;Drug: Endotoxin<br>* intravenously<br>* Other names: 2 ng/kg E. coli reference endotoxin 11:H 10:K negative;|
| Placebo Comparator: Placebo<br>Placebo (saline 0.9%) infusion followed by administration of Endotoxin 2ng/kg | Drug: Endotoxin<br>* intravenously<br>* Other names: 2 ng/kg E. coli reference endotoxin 11:H 10:K negative;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutrophil phenotype and redistribution |  | 8 hrs after LPS administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |