Anti-Inflammatory Effect of Statins in the Human Endotoxin Model
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ClinicalTrials.gov Identifier: NCT00309374 |
Recruitment Status :
Completed
First Posted : March 31, 2006
Last Update Posted : January 5, 2007
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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 |
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.
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 |

- monocyte CRP production
- leukocyte mRNA expression profiles (human genome GeneChip arrays)
- various inflammation and coagulation parameters
- platelets
- endothelial progenitor cells
- adverse events

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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

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 ClinicalTrials.gov identifier (NCT number): NCT00309374
Austria | |
Medical University of Vienna, Dept. of Clinical Pharmacology | |
Vienna, Austria |
Principal Investigator: | Michael Wolzt, MD | Medical University of Vienna |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov 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 |
LPS Statins leukocyte mRNA expression profiles |
Endotoxemia Bacteremia Sepsis Infection Toxemia Systemic Inflammatory Response Syndrome Inflammation Pathologic Processes Rosuvastatin Calcium |
Simvastatin Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors |