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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-002222-46 | EudraCT Number |
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| Name | Class |
|---|---|
| UMC Utrecht | OTHER |
| Prothya Biosolutions | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| C1-esterase inhibitor | Active Comparator | C1-esterase inhibitor 100 U/kg infusion followed by administration of Endotoxin 2ng/kg |
|
| Placebo | Placebo Comparator | Placebo (saline 0.9%) infusion followed by administration of Endotoxin 2ng/kg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| C1-esterase inhibitor | Drug | intravenously |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Neutrophil phenotype and redistribution | 8 hrs after LPS administration |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hans Hoeven, Prof | UMC Nijmegen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radboud University | Nijmegen | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28515092 | Derived | Tak T, Wijten P, Heeres M, Pickkers P, Scholten A, Heck AJR, Vrisekoop N, Leenen LP, Borghans JAM, Tesselaar K, Koenderman L. Human CD62Ldim neutrophils identified as a separate subset by proteome profiling and in vivo pulse-chase labeling. Blood. 2017 Jun 29;129(26):3476-3485. doi: 10.1182/blood-2016-07-727669. Epub 2017 May 17. |
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| ID | Term |
|---|---|
| D019446 | Endotoxemia |
| D007249 | Inflammation |
| D018805 | Sepsis |
| ID | Term |
|---|---|
| D016470 | Bacteremia |
| D007239 | Infections |
| D014115 | Toxemia |
| D018746 | Systemic Inflammatory Response Syndrome |
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| ID | Term |
|---|---|
| D050718 | Complement C1 Inhibitor Protein |
| C472494 | let-363 protein, C elegans |
| D004731 | Endotoxins |
| ID | Term |
|---|---|
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D003174 | Complement C1 Inactivator Proteins |
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| Endotoxin | Drug | intravenously |
|
|
| D010335 |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D015843 |
| Serpins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D003169 | Complement Inactivator Proteins |
| D003165 | Complement System Proteins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |