Anti-inflammatory effect of statins in the human endotoxin model

INTERVENTION: Trade Name: Zocord 80 mg ‐ Filmtabletten Pharmaceutical Form: Film‐coated tablet Pharmaceutical form of the placebo: Capsule, soft Route of administration of the placebo: Oral use Trade Name: CRESTOR 40 mg ‐ Filmtabletten Pharmaceutical Form: Film‐coated tablet Pharmaceutical form of the placebo: Capsule, soft Route of administration of the placebo: Oral use Product Name: USP Reference Standard Endotoxin 10000 U Pharmaceutical Form: Solution for injection CONDITION: Healthy volunteers are tested in an endotoxemia model PRIMARY OUTCOME: Main Objective: ‐To determine the effect of HMG‐CoA reductase inhibitor pretreatment on inflammation and coagulation activation in human endotoxemia.; Primary end point(s): Thrombus formation (D‐dimer content of degraded ex vivo thrombus), monocyte CRP production, leukocyte mRNA expression profiles (human genome GeneChip arrays) Secondary Objective: ‐To investigate if anti‐inflammatory effects are similar between two different statins.; ‐To study genome‐wide effects on the leukocyte transcriptome induced by (i) statin pretreatment, (ii) low‐dose endotoxemia, and (iii) the anti‐inflammatory effects if the statins INCLUSION CRITERIA: ‐Men aged between 18 and 45 years ‐Nonsmokers or smokers <10 cig/d ‐Body mass index between 15th and 85th percentile (Must et al. 1991) ‐Normal findings in medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range