Healthy
Conditions
Keywords
Statins, anti-inflammatory, Healthy subjects study
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.
Interventions
DRUGRosuvastatin
Healthy subjects received rosuvastatin 20 mg orally for 3 weeks. Inflammatory markers measured pre- and post- rosuvastatin treatment.
Sponsors
University of Nebraska
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
19 Years to 39 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
Countries
United States
Participant flow
Recruitment details
A total of 20 subjects were consented between 11/15/2010 and on 8/4/2011.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Baseline laboratories outside of normal limits (screen fails). | 4 |
Baseline characteristics
| Characteristic | Rosuvastatin |
|---|---|
| Age, Continuous | 27 years |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 16 |
| other Total, other adverse events | 1 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
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.
Time frame: Before and after three weeks of treatment with rosuvastatin
Population: A total of 16 healthy subjects who met inclusion/exclusion criteria
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pre-treatment Tlr-4 Expression | Toll-like Receptor 4 Expression Pre- and Post-Treatment | 12.37 % tlr expression (monocytes) | Standard Deviation 9.8 |
| Post-treatment Trl-4 Monocyte Expression | Toll-like Receptor 4 Expression Pre- and Post-Treatment | 6.36 % tlr expression (monocytes) | Standard Deviation 4.8 |
Secondary
Interleukin-6
Interleukin-6 inflammatory cytokine which will be released after LPS treatment of blood
Time frame: Before (baseline) and after 3 weeks of rosuvastatin treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pre-treatment Tlr-4 Expression | Interleukin-6 | 4.8 pg/ml | Standard Deviation 1.3 |
| Post-treatment Trl-4 Monocyte Expression | Interleukin-6 | 4.1 pg/ml | Standard Deviation 1 |
Secondary
Interleukin-8
Interleukin-8 an inflammatory cytokine which will be releases after LPS treatment.
Time frame: measured in LPS treated blood before and after 3 weeks of Rosuvastatin treatment
Population: 16 subjects that met the inclusion/exclusion criteria the pre-post analysis allowed the use of paired T-test
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pre-treatment Tlr-4 Expression | Interleukin-8 | 155 pg/ml | Standard Deviation 45 |
| Post-treatment Trl-4 Monocyte Expression | Interleukin-8 | 125 pg/ml | Standard Deviation 27 |
Secondary
Tumor Necrosis Factor (TNF)
Inflammatory cytokine generated after treatment of whole blood collected before and after rosuvastatin treatment
Time frame: Pre and post 3 weeks of rosuvastatin treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pre-treatment Tlr-4 Expression | Tumor Necrosis Factor (TNF) | 145 pg/ml | Standard Deviation 52 |
| Post-treatment Trl-4 Monocyte Expression | Tumor Necrosis Factor (TNF) | 92 pg/ml | Standard Deviation 25 |