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Anti-Inflammatory Effect of Statins in the Human Endotoxin Model

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00309374
Recruitment Status : Completed
First Posted : March 31, 2006
Last Update Posted : January 5, 2007
Information provided by:
Medical University of Vienna

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.

Condition or disease Intervention/treatment Phase
Endotoxemia Drug: LPS 2ng/kg intravenous bolus Drug: Simvastatin 80mg; administered daily p.o. over 5 days Drug: Rosuvastatin 40mg; administered daily p.o. over 5 days Phase 1

Detailed Description:

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 will receive LPS (2 ng/kg i.v.). Inflammatory protein expression and coagulation activation will be assessed on Day 1 and Day 5 of each period. Washout-time between treatment periods will be ≥6 weeks.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: Anti-Inflammatory Effect of Statins in the Human Endotoxin Model
Study Start Date : March 2006
Study Completion Date : July 2006

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. monocyte CRP production
  2. leukocyte mRNA expression profiles (human genome GeneChip arrays)

Secondary Outcome Measures :
  1. various inflammation and coagulation parameters
  2. platelets
  3. endothelial progenitor cells
  4. adverse events

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Men aged between 18 and 45 years
  • Nonsmokers or smokers <5 cig/d
  • Body mass index between 18 and 30; respectively weight ≤ 95 kilograms
  • Normal findings in medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant

Exclusion Criteria:

  • Regular use of medication, abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study
  • Evidence of hypertension, pathologic hyperglycemia, hyperlipidemia
  • Treatment in the previous 3 weeks with any drug
  • Symptoms of a clinically relevant illness in the 3 weeks before the first study day
  • History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with distribution, metabolism or excretion of study drugs
  • Blood donation during the previous 3 weeks
  • History of hypersensitivity to the trial drug or to drugs with a similar chemical structure

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00309374

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Medical University of Vienna, Dept. of Clinical Pharmacology
Vienna, Austria
Sponsors and Collaborators
Medical University of Vienna
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Principal Investigator: Michael Wolzt, MD Medical University of Vienna
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00309374    
Other Study ID Numbers: EK291/2005Version2.0
First Posted: March 31, 2006    Key Record Dates
Last Update Posted: January 5, 2007
Last Verified: January 2007
Keywords provided by Medical University of Vienna:
leukocyte mRNA expression profiles
Additional relevant MeSH terms:
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Systemic Inflammatory Response Syndrome
Pathologic Processes
Rosuvastatin Calcium
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors