Clinical Trial: Anti-Inflammatory Effect of Statins in the Human Endotoxin Model

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Anti-Inflammatory Effect of Statins in the Human Endotoxin Model

Brief Summary: The purpose of this study is to determine the effects of HMG-CoA reductase inhibitor pretreatment on inflammation and coagulation activation in human endotoxemia.

Detailed Summary:

The beneficial effect of lipid lowering in cardiovascular disease is well established. Statin potently reduce elevated cholesterol levels but also exert pleiotropic other effects such as improvement of inflammation-induced vascular dysfunction, upregulation of endothelial nitric oxide synthase, yield antiinflammatory and antioxidant properties and lower tissue factor (TF) expression on peripheral blood mononuclear cells (PB-MNC) in vivo. The mechanism of action for these effects remains unclear, but is already seen after short term treatment and was independent of cholesterol reduction. Following endotoxin administration to healthy humans, the systemic response includes the activation of inflammation by cytokines, mainly IL-1, IL-6, THF-α and INF-γ, activation of the clotting system with enhanced thrombin generation, and vascular dysfunction, as demonstrable by an impaired response to vasoconstrictors. Low dose endotoxemia therefore serves as an adequate model for acute inflammation and the interaction of the three systems.

The goal of this study is to determine the effect of HMG-CoA reductase inhibitor pretreatment on inflammation and coagulation activation in human endotoxemia and to investigate if anti-inflammatory effects are similar between two different statins. Further, we plan 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.

The study will be carried out as a randomized placebo controlled double-blind threeway crossover three period study. Subjects will receive three treatment periods (Day 1 - Day 5) in randomized order consisting of 5 days oral Simvastatin (80 mg/day), 5 days oral Rosuvastatin (40 mg/day) and 5 days adequate placebo. On Day 5 of each study period, subjects wil
Sponsor: Medical University of Vienna

Current Primary Outcome:

  • monocyte CRP production
  • leukocyte mRNA expression profiles (human genome GeneChip arrays)


Original Primary Outcome:

  • monocyt CRP production
  • leukocyte mRNA expression profiles (human genome GeneChip arrays)


Current Secondary Outcome:

  • various inflammation and coagulation parameters
  • platelets
  • endothelial progenitor cells
  • adverse events


Original Secondary Outcome: Same as current

Information By: Medical University of Vienna

Dates:
Date Received: March 30, 2006
Date Started: March 2006
Date Completion: July 2006
Last Updated: January 4, 2007
Last Verified: January 2007