Blood poisening sepsis
Conditions
Interventions
The volunteers will be randomized to 5 intervention groups.
1. iron loading + placebo prio to endotoxemia (N=12):
T=-2: Placebo orally
T=-1: iron sucrose (Venofer®) 1.25 mg/kg i.v.
T= 0: 2ng/kg LPS
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 or anti-oxidant vitamin supplements - History of allergic reaction to iron preparations or iron chelators. - Smoking - History of frequent vaso-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 1st 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 - Subjects with elevated bilirubin levels >20 umol/l - Dyslipidemia or elevated glucose level - Positive HIV serology - Immune deficiency - Febrile illness in the week before the LPS challenge - Participation in a drug trial or donation of blood 3 months prior to the LPS challenge - Participation in a previous study in which LPS was administered.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of the study is the concentraion of circulation cytokines after administraion of LPS in the presence of iron sucrose (Venofer®), Deferasirox (Exjade®) or placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objectives are: Markers of iron homeastasis: - plasma levels of hepcidin, transferrin, soluable transferrin receptor, serum iron, total ironbindingcapacity, GDF15. - expression of these same proteins in isolated monocytes on mRNA and protein level. Markers of oxidative stress in whole blood/plasma: - neutrofil burst, concentration of thiols, TBARS, carbonyls, superoxide dysmutase, glutathion peroxidase, hemoxygenase-1 mRNA and protein. Subclinical organ damage: - Endothelial dysfunction measured as the change in forearm blood flow in reaction to intra-arterially administration of vasoactive mediaction (acetylcholine, nitroglycerine en norepinephrine) - Subclinical kidneydamage (measured as excrestion of tubular proteins GST-alpha and pi in the urine) | — |
Countries
Netherlands
Outcome results
None listed