septic shock systemic inflammation
Conditions
Interventions
Subjects will be tested in a cross-over design in 2 separate sessions, 2-4
weeks apart. Subjects will receive 150 mg GTS-21 or placebo orally tid on the
day before LPS injection and a single oral do
Sponsors
Universitair Medisch Centrum Sint Radboud
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: healthy male volunteers (no medical history, no medication) age 18-35 years non-smokers
Exclusion criteria
Exclusion criteria: Use of any medication Smoking History, signs or symptoms of cardiovascular disease (Family) history of cerebrovascular disease Previous vagal collaps 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 test
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| the concentration of TNF after the administration of LPS in the absence and presence of GTS-21. | — |
Secondary
| Measure | Time frame |
|---|---|
| Concentration of pro- and anti-inflammatory cytokines, HMGB-1 AChR and TLR expression on circulating monocytes Leucocyte number, C-reactive protein concentration Severity of clinical symptoms, hemodynamic parameters Ex-vivo TLR receptor stimulation assays on whole blood to measure cytokines, AChR and TLR expression. Circulating endothelial cells and markers of endothelial damage (adhesion molecules). Urine excretion of markers of proximal (GSTA1-1) and distal (GSTP1-1) renal tubular damage. Brain specific proteins S100β, NSE, GFAP Vagal activity as measured by heart rate variability analysis | — |
Countries
Netherlands
Outcome results
None listed