The effects of iron loading and iron chelation during human endotoxemia.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 54

Inclusion Criteria

Age >= 18 and <= 35 yrs
Male
Healthy

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 < 100 or RR diastolic < 50)
- Renal impairment (defined as plasma creatinin >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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of the study is the concentraion of circulation cytokines<br /><br>after administraion of LPS in the presence of iron sucrose (Venofer®),<br /><br>Deferasirox (Exjade®) or placebo.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary objectives are:<br /><br><br /><br>Markers of iron homeastasis:<br /><br>- plasma levels of hepcidin, transferrin, soluable transferrin receptor, serum<br /><br>iron, total ironbindingcapacity, GDF15.<br /><br>- expression of these same proteins in isolated monocytes on mRNA and protein<br /><br>level.<br /><br><br /><br>Markers of oxidative stress in whole blood/plasma:<br /><br>- neutrofil burst, concentration of thiols, TBARS, carbonyls, superoxide<br /><br>dysmutase, glutathion peroxidase, hemoxygenase-1 mRNA and protein.<br /><br><br /><br>Subclinical organ damage:<br /><br>- Endothelial dysfunction measured as the change in forearm blood flow in<br /><br>reaction to intra-arterially administration of vasoactive mediaction<br /><br>(acetylcholine, nitroglycerine en norepinephrine)<br /><br>- Subclinical kidneydamage (measured as excrestion of tubular proteins<br /><br>GST-alpha and pi in the urine)</p><br>