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

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

Study Overview

• Status: Completed
• Conditions: Healthy Controls
• Intervention / Treatment: Drug: Atorvastatin; Drug: Pneumovax 23; Other: Placebo (lactose pill)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Clinical Translational Research Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

24 subjects are healthy volunteers between the ages of 21 and 40.

Exclusion Criteria:

1. Pregnant, planning to become pregnant, breastfeeding
2. 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
3. Taking any immunosuppressive drugs including azathioprine, methotrexate, TNF inhibitors, cyclophosphamide, antimalarials, or sulfasalazine
4. 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
5. 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
6. Latex allergy or previous allergic reaction or severe side effects from any vaccine
7. 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
8. BMI over 30, abnormal values on lipid panel or liver function test
9. Failure to pass pre-study medical screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the effect of atorvastatin treatment on immune-regulatory gene expression.	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

Collaborators and Investigators

• Sponsor: University of Florida

Publications and helpful links

General Publications

• Wildes TJ, Grippin A, Fasanya H, Dyson KA, Brantly M. Effect of atorvastatin on humoral immune response to 23-valent pneumococcal polysaccharide vaccination in healthy volunteers: The StatVax randomized clinical trial. Vaccine. 2019 Feb 28;37(10):1313-1324. doi: 10.1016/j.vaccine.2019.01.023. Epub 2019 Jan 25.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: March 24, 2014
• First Submitted That Met QC Criteria: March 24, 2014
• First Posted (Estimate): March 27, 2014

Study Record Updates

• Last Update Posted (Estimate): September 28, 2015
• Last Update Submitted That Met QC Criteria: September 25, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Health Controls
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Immunologic Factors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: IRB201400208