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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rosuvastatin | Healthy subjects received rosuvastatin 20 mg orally for 3 weeks. Inflammatory markers measured pre and post rosuvastatin treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rosuvastatin | Drug | Healthy subjects received rosuvastatin 20 mg orally for 3 weeks. Inflammatory markers measured pre- and post- rosuvastatin treatment. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Toll-like Receptor 4 Expression Pre- and Post-Treatment | Toll-like Receptor 4 (TLR-4) expression on monocytes in whole blood pre- and post- 3 weeks of rosuvastatin treatment. | Before and after three weeks of treatment with rosuvastatin |
| Measure | Description | Time Frame |
|---|---|---|
| Tumor Necrosis Factor (TNF) | Inflammatory cytokine generated after treatment of whole blood collected before and after rosuvastatin treatment | Pre and post 3 weeks of rosuvastatin treatment |
| Interleukin-6 |
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Inclusion Criteria:
Exclusion Criteria:
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20 healthy subjects
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| Name | Affiliation | Role |
|---|---|---|
| Timothy R McGuire, PharmD | University of Nebraska | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Nebraska Medical Center, College of Pharmacy | Omaha | Nebraska | 68198-6045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16614188 | Background | Wickelgren I. Immunology. Targeting the tolls. Science. 2006 Apr 14;312(5771):184-7. doi: 10.1126/science.312.5771.184. No abstract available. | |
| 18263570 | Background | Falagas ME, Makris GC, Matthaiou DK, Rafailidis PI. Statins for infection and sepsis: a systematic review of the clinical evidence. J Antimicrob Chemother. 2008 Apr;61(4):774-85. doi: 10.1093/jac/dkn019. Epub 2008 Feb 7. |
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A total of 20 subjects were consented between 11/15/2010 and on 8/4/2011.
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| ID | Title | Description |
|---|---|---|
| FG000 | Rosuvastatin | 20 subjects were consented to receive rosuvastatin 20 mg tablets orally every day for three weeks. 16 of the 20 received study drug with four being excluded due to baseline laboratory abnormalities. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The 16 patients that met inclusion/exclusion criteria were Caucasian.
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| ID | Title | Description |
|---|---|---|
| BG000 | Rosuvastatin | Single arm non-therapeutic study where all subjects who ruled in for study participation (based on baseline laboratories and clinical assessment) received rosuvastatin 20 mg tablets for three weeks. Inflammatory markers Toll-like Receptor 4, tumor necrosis factor, Interleukin 6, Interleukin 8 (tlr-4, TNF, IL-6, IL-8) were measured at baseline prior to rosuvastatin administration and after treatment to compare the effect of rosuvastatin on inflammatory markers. The primary outcome was the %tlr positive monocytes. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Toll-like Receptor 4 Expression Pre- and Post-Treatment | Toll-like Receptor 4 (TLR-4) expression on monocytes in whole blood pre- and post- 3 weeks of rosuvastatin treatment. | A total of 16 healthy subjects who met inclusion/exclusion criteria | Posted | Mean | Standard Deviation | % tlr expression (monocytes) | Before and after three weeks of treatment with rosuvastatin |
|
Collected over 3 weeks for each subject
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rosuvastatin | Single arm non-therapeutic study | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Muscle pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Timothy R McGuire | University of Nebraska Medical Center | 402-651-2496 | trmcguir@unmc.edu |
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| ID | Term |
|---|---|
| D000068718 | Rosuvastatin Calcium |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
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|
Interleukin-6 inflammatory cytokine which will be released after LPS treatment of blood
| Before (baseline) and after 3 weeks of rosuvastatin treatment |
| Interleukin-8 | Interleukin-8 an inflammatory cytokine which will be releases after LPS treatment. | measured in LPS treated blood before and after 3 weeks of Rosuvastatin treatment |
| 16443229 | Background | Niessner A, Steiner S, Speidl WS, Pleiner J, Seidinger D, Maurer G, Goronzy JJ, Weyand CM, Kopp CW, Huber K, Wolzt M, Wojta J. Simvastatin suppresses endotoxin-induced upregulation of toll-like receptors 4 and 2 in vivo. Atherosclerosis. 2006 Dec;189(2):408-13. doi: 10.1016/j.atherosclerosis.2005.12.022. Epub 2006 Jan 26. |
| 19205663 | Background | Novack V, Eisinger M, Frenkel A, Terblanche M, Adhikari NK, Douvdevani A, Amichay D, Almog Y. The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: a randomized double-blind placebo controlled clinical trial. Intensive Care Med. 2009 Jul;35(7):1255-60. doi: 10.1007/s00134-009-1429-0. Epub 2009 Feb 11. |
| 18068482 | Background | Wang CY, Liu PY, Liao JK. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol Med. 2008 Jan;14(1):37-44. doi: 10.1016/j.molmed.2007.11.004. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Secondary | Tumor Necrosis Factor (TNF) | Inflammatory cytokine generated after treatment of whole blood collected before and after rosuvastatin treatment | Posted | Mean | Standard Deviation | pg/ml | Pre and post 3 weeks of rosuvastatin treatment |
|
|
|
| Secondary | Interleukin-6 | Interleukin-6 inflammatory cytokine which will be released after LPS treatment of blood | Posted | Mean | Standard Deviation | pg/ml | Before (baseline) and after 3 weeks of rosuvastatin treatment |
|
|
|
| Secondary | Interleukin-8 | Interleukin-8 an inflammatory cytokine which will be releases after LPS treatment. | 16 subjects that met the inclusion/exclusion criteria the pre-post analysis allowed the use of paired T-test | Posted | Mean | Standard Deviation | pg/ml | measured in LPS treated blood before and after 3 weeks of Rosuvastatin treatment |
|
|
|
| 16 |
| 0 |
| 16 |
| 1 |
| 16 |
| insomnia | General disorders | Non-systematic Assessment |
|
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| D006845 |
| Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |