Effect of Rosuvastatin Response in Healthy Subjects: Potential Mechanisms of Anti-inflammatory Effects

Completed

Conditions: Healthy

Interventions: Drug: Rosuvastatin

Registration Number: NCT00874757

Lead Sponsor: University of Nebraska

Brief Summary: The purpose of this study is to see whether Statin drugs will act as anti-inflammatories. The investigators will study this potential anti-inflammatory activity in healthy subjects.

Detailed Description: After providing consent healthy subjects (N=20) completed a health and drug inventory questionnaire and had blood samples drawn to measure baseline electrolytes, kidney function, liver function, and creatine kinase to determine study eligibility. Blood samples were also collected to analyze baseline inflammatory markers (tlr-4 monocyte expression and cytokine production). Patients received 20 mg daily of rosuvastatin for 3 weeks followed by blood collection, and the measurement of inflammatory markers repeated. Whole blood samples were analyzed by flow-cytometry to determine percent expression of tlr-4 on monocytes which was the primary inflammatory marker for the study. Secondary inflammatory markers tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-8 (IL-8) were measured after blood was incubated ex-vivo with lipopolysaccharide (LPS) for 3 hours. LPS induction experiments were performed on blood from pre and post rosuvastatin treatment. Finally, blood lipid profiles (cholesterol, low density lipoprotein (LDL), very low-density lipoprotein (VLDL), and high density lipo protein (HDL), were assessed both pre and post rosuvastatin treatment. End of study (after 3 weeks of rosuvastatin treatment) electrolytes, kidney function, liver function, and creatine kinase (CK) were measured to determine any changes as a result of rosuvastatin treatment. In addition to pre and post safety assessment a phone call was made to evaluate rosuvastatin side effects at the midpoint of the three-week treatment period.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 20

Inclusion Criteria

Healthy male non-asian subjects

Exclusion Criteria

Patients with increased liver function tests, elevated serum creatine, patients on anti-inflammatory or immunomodulating drugs

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Rosuvastatin	Rosuvastatin	Healthy subjects received rosuvastatin 20 mg orally for 3 weeks. Inflammatory markers measured pre and post rosuvastatin treatment.

Primary Outcome Measures

Name	Time	Method
Toll-like Receptor 4 Expression Pre- and Post-Treatment	Before and after three weeks of treatment with rosuvastatin	Toll-like Receptor 4 (TLR-4) expression on monocytes in whole blood pre- and post- 3 weeks of rosuvastatin treatment.

Secondary Outcome Measures

Name	Time	Method
Interleukin-8	measured in LPS treated blood before and after 3 weeks of Rosuvastatin treatment	Interleukin-8 an inflammatory cytokine which will be releases after LPS treatment.
Tumor Necrosis Factor (TNF)	Pre and post 3 weeks of rosuvastatin treatment	Inflammatory cytokine generated after treatment of whole blood collected before and after rosuvastatin treatment
Interleukin-6	Before (baseline) and after 3 weeks of rosuvastatin treatment	Interleukin-6 inflammatory cytokine which will be released after LPS treatment of blood