The Effect of Short-term Atorvastatin Treatment on Immune Responses to Pneumovax 23

Study Overview
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Brief Summary
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The purpose of this research study is to: Improve the effectiveness of vaccinations by identifying the effect of cholesterol medication, statins, on immune responses.

Detailed Description
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Due to the anti-inflammatory action of statins, it was proposed that statin treatment would decrease the efficacy of vaccination. This response has yet to be explored following a primary vaccination such as pneumococcal pneumonia. In this study, healthy volunteers will be divided into 2 arms receiving treatment for 28 days: 40 mg atorvastatin or placebo. Antibody titer for 23 serotypes, complete blood count (CBC), high-sensitivity c-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), lipids, cytokines (TNF-alpha, IFN-gamma, interleukins, etc.) and key membrane receptors (toll-like receptors, etc.) will be measured for baseline before statin or placebo treatment. On day 7 of treatment, pre-vaccination measures of the above parameters will be taken and an immune response will be induced in all groups using Pneumovax 23 at Day 7. On days 8, 14, 21, and 28 post-vaccination measures will be compared to baseline and between groups.

Official Title
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The Effect of Short-term Atorvastatin Treatment on Immune Responses to Pneumovax 23

Conditions
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Healthy Controls

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: Pneumovax 23
* Other: Placebo (lactose pill)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 24 subjects are healthy volunteers between the ages of 21 and 40. Exclusion Criteria: Pregnant, planning to become pregnant, breastfeeding Taking any of the following medications at time of study: antacids, antifungals, antioxidants, colestipol, cyclosporine, digoxin, erythromycin, fibric acid derivatives, niacin, oral contraceptives containing norethindrone or ethinyl estradiol, statins, steroids Taking any immunosuppressive drugs including azathioprine, methotrexate, TNF inhibitors, cyclophosphamide, antimalarials, or sulfasalazine Currently have or history of cardiovascular disease, diabetes, diphtheria, high blood pressure, high cholesterol, immunodeficiencies, kidney disease, liver disease, low blood pressure, muscular disease, seizure disorders, systemic lupus erythematosus or other systemic autoimmune disorders Not immunized in childhood against streptococcus pneumoniae; received pneumovax vaccine within past year, or received 2 or more pneumovax boosters within the past 5 years Latex allergy or previous allergic reaction or severe side effects from any vaccine Heavy drinking (more than 15 drinks/week), illegal drug use within past six months, unwillingness to abstain from alcohol, unwillingness to abstain from tobacco products (dip, cigarettes, cigars, electronic cigarettes, etc.), illegal drugs, or grapefruit juice for duration of study BMI over 30, abnormal values on lipid panel or liver function test Failure to pass pre-study medical screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pneumovax-Atorvastatin<br>10-person arm receiving treatment for 28 days: 40 mg atorvastatin, taken orally, once daily, for 28 days. Pneumovax 23 injected once, intramuscularly at Day 7. | Drug: Atorvastatin<br>* 10-person arm receiving treatment for 28 days: 40 mg atorvastatin, taken orally, once daily, for 28 days.<br>* Other names: Lipitor;Drug: Pneumovax 23<br>* Pneumovax 23 injected once, intramuscularly at Day 7.<br>* Other names: 23-valent pneumococcal polysaccharide vaccine;|
| Placebo Comparator: Pneumovax-Placebo<br>10-person arm receiving treatment for 28 days: Placebo (lactose pill), taken orally, once daily for 28 days. Pneumovax 23 injected once, intramuscularly at Day 7. | Drug: Pneumovax 23<br>* Pneumovax 23 injected once, intramuscularly at Day 7.<br>* Other names: 23-valent pneumococcal polysaccharide vaccine;Other: Placebo (lactose pill)<br>* 10-person arm receiving treatment for 28 days: Placebo (lactose pill), taken orally, once daily for 28 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the effect of atorvastatin treatment on pneumococcal antigen specific antibody production. | The 24 subjects will be randomized into 2 groups of 12 individuals (6 per gender) and will be assigned to receive either atorvastatin treatment (40mg/day) or placebo (lactose pill) control. Subjects will be asked to fast after midnight prior to any morning blood draws. On day 1 of treatment, blood will be drawn for a baseline. Treatment with either atorvastatin or placebo will begin on day one and will continue until day 28. Subjects will be instructed to take the study medication once a day at the same time each day. On day seven of treatment, subjects will be immunized with Pneumovax 23, administered intramuscularly into the arm. Blood will be drawn at several time points following Pneumovax 23 administration. Measurements on blood will be made to determine the effect of statins on immune factor gene expression, serum protein levels, as well as at the cellular level. | approximately 49 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the effect of atorvastatin treatment on immunogenic cytokine levels following pneumococcal vaccination. | The 24 subjects will be randomized into 2 groups of 12 individuals (6 per gender) and will be assigned to receive either atorvastatin treatment (40mg/day) or placebo (lactose pill) control. Subjects will be asked to fast after midnight prior to any morning blood draws. On day 1 of treatment, blood will be drawn for a baseline. Treatment with either atorvastatin or placebo will begin on day one and will continue until day 28. Subjects will be instructed to take the study medication once a day at the same time each day. On day seven of treatment, subjects will be immunized with Pneumovax 23, administered intramuscularly into the arm. Blood will be drawn at several time points following Pneumovax 23 administration. Measurements on blood will be made to determine the effect of statins on immune factor gene expression, serum protein levels, as well as at the cellular level. | approximately 49 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Health Controls