The effects of bilirubin infusion on the innate immune response during human endotoxemia.;A parallel open label placebo controlled pilot study.

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 22

Inclusion Criteria

-Age >= 18 and <= 35 years
-Male
-Healthy

Exclusion Criteria

-Use of any medication or anti-oxidant vitamin supplements.
-History of allergic reaction to albumin or any other drug used in the study.
-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 1st degree (or higher degree) atrioventricular block or a complex bundle branch block.
- Hypertension (defined as a repeated measurement of RR systolic > 160 or RR diastolic > 90 mmHg).
- Hypotension (defined as RR systolic < 100 or RR diastolic < 50 mmHg).
- Renal impairment (defined as plasma creatinin >120 µmol/l).
- Liver enzyme abnormalities or positive hepatitis B serology.
- Subjects with a total bilirubin level above 15 µmol/L and a normal direct bilirubin level suggesting Gilbert Syndrome.
- Positive HIV serology or any other obvious disease associated with immune deficiency.
- Febrile illness in the week before the experiment.
- Participation in a drug trial or donation of blood 3 months prior to the LPS challenge.
- Inability to understand the nature and extent of the trial and the procedures required.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The main study parameter is the concentration of circulating cytokines at<br /><br>different time points following LPS administration in the absence or presence<br /><br>of hyperbilirubinemia. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- pro-anti oxidant balance during human endotoxemia in the absence or presence<br /><br>of hyperbilirubinemia<br /><br>- endothelial dysfunction during human endotoxemia in the absence or presence<br /><br>of hyperbilirubinemia as assessed by the measurement of the response to<br /><br>vasodilators acetylcholine and nitroglycerin. Furthermore, the release of<br /><br>vascular adhesion molecules indicating activation of the endothelium will be<br /><br>measured<br /><br>- subclinical renal damage known to occur during human endotoxemia in the<br /><br>absence or presence of hyperbilirubinemia<br /><br>- the interplay between HO-1, NO and bilirubin during human endotoxemia</p><br>