pulmonary inflammation gram negative pulmonary infections recombinant activated protein C pulmonary effects of lipopolysaccharide (LPS) blood coagulation during pulmonary inflammation longinflammatie gramnegatieve longontstekingen recombinant geactiveerd proteine C pulmonale effecten van LPS bloedstolling tijdens pulmonale inflammatie
Conditions
Interventions
1. Dose-escalation study:
Healthy volunteers will be challenged with LPS (4
ng/kg) into a subsegment of both lungs
in one lung segment LPS will be
combined with rhAPC, whereas in the contralateral lung segment LPS will be
combined with normal saline. Six hours later a bilateral bronchoalveolar
lavage (BAL) will be
in 12
of these subjects LPS will be combined with rhAPC (dose determined in the
dose-escalation study), in the other 12 subjects LPS will be combined with
saline. In addition, 12 subjects will receive
Sponsors
Prof. Dr. Tom van der Poll, principal investigator. Center of Experimental Molecular Medicine, AMC-UvA, Amsterdam, The Netherlands
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male, 18-35 years of age 2. No clinically significant findings during physical examination and hematological and biochemical screening 3. Normal spirometry and ECG 4. Able to communicate well with the investigator and to comply with the requirements of the study 5. No medication 6. Written informed consent 7. No smoking
Exclusion criteria
Exclusion criteria: 1. Known diseases 2. A history of smoking within the last six months, or regular consumption of greater than three units of alcohol per day 3. Administration of any investigational drug within 30 days of study initiation 4. Donation of blood within 60 days, or loss of greater than 400 ml of blood within 12 weeks of study initiation 5. History of enhanced bleeding tendency 6. History of heparin-induced thrombocytopenia 7. History of serious drug-related reactions, including hypersensitivity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine whether direct intrapulmonary delivery of rhAPC can inhibit LPS-induced lung inflammation, thereby avoiding systemic APC effects | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Neutrophil responses 2. Response of alveolar macrophages 3. Activation of the cytokine and chemokine network 4. Activation of coagulation and fibrinolysis | — |
Contacts
Public ContactLiesbeth Kager
Academic Medical Center (AMC) Meibergdreef 9 room F0-117
Outcome results
None listed