Blood poisoning sepsis
Conditions
Interventions
All subjects (n=18) will receive an intravenous bolus of endotoxin (LPS derived
from E coli O:113, 2 ng/kg) twice, with an interval of 6 days (LPS
administration on day 1 and 7). Subjects will recei
(100 µg/day subcutaneously, n=6) or placebo
(NaCl 0.9% subcutaneously, n=6) in a randomized, double-blind manner on day 2,
4 and 6.
Sponsors
Universitair Medisch Centrum Sint Radboud
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Age >=18 and
Exclusion criteria
Exclusion criteria: - Use of any medication - History of allergic reaction to GM-CSF/ IFN-γ. - Smoking. - Previous spontaneous vagal collapse. - History, signs or symptoms of cardiovascular disease. - (Family) history of myocardial infarction or stroke under the age of 65 years. - Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complex bundle branch block. - Hypertension (defined as RR systolic > 160 or RR diastolic > 90). - Hypotension (defined as RR systolic 120 µmol/l). - Liver enzyme abnormalities or positive hepatitis serology. - Positive HIV serology or medical history of any other obvious disease associated with immune deficiency. - Febrile illness during the week before the LPS challenge. - Participation in a drug trial or donation of blood 3 months prior to the LPS challenge. - Chronic hiccups (defined as hiccups longer than 15 minutes in the past 6 months) - Pre-existent muscle disease (congenital or acquired) or diseases / disorders know to be associated with myopathy including diabetes and auto-immune diseases. - Pre-existent lung disease - Upper airway / esophageal pathology - Recent (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The main study parameter is the difference in the LPS-induced increase in plasma TNF-a concentration between day 1 and day 7. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary study parameters include plasma levels of other inflammatory mediators, ex vivo production of inflammatory mediators by stimulated leukocytes, monocyte HLA-DR expression, NF*B activation by ROS/RNS, transcriptional activity of leukocytes, changes in phenotype or gene expression caused by mechanisms other than changes in the underlying DNA sequence (epigenetics), urinary markers of tubular injury, twitch transdiaphragmatic pressure, illness score, mean arterial pressure, heart rate and temperature. | — |
Countries
Netherlands
Outcome results
None listed