Impact of Metformin on Immunity

The objective of this study is to determine whether metformin (MET) can improve the immune
response to the pneumococcal conjugate vaccine (PCV-13) in older adults, and if this effect
is mediated by the gut microbiota.

The proposed research projects will provide the necessary pilot data for future, more
definitive, studies that will evaluate the impact of immunomodulatory therapies, such as MET
therapy, on the aging immune system. The specific aims are:

Aim 1. Compare PCV13 vaccine response in elderly adults (≥63 years of age) treated with MET
vs. placebo. For this study, 50 elderly volunteers will be enrolled and randomly assigned to
receive MET or placebo. The hypothesis that MET can improve vaccine responsiveness by
measuring serotype-specific IgG concentrations before and 30 days after PCV13 administration
will be tested.

Aim 2. Determine whether the frequencies of immunophenotypes differ between elderly adults
treated with MET vs. placebo. The mechanisms of MET's effect on the immune system by
comparing immunophenotypes of MET and placebo groups between baseline and prior to PCV13 and
between baseline and 30 days after PCV13 administration will be explored.

Inclusion Criteria:

1. Age 63 to 89 years of age

2. No history of pneumococcal vaccinations

3. Able to take oral medications

4. Able to provide informed consent

5. Not currently taking metformin

Exclusion Criteria:

1. Previous vaccination with any pneumococcal vaccine

2. Metformin within the last 6 months

3. Contraindication for PCV13

4. History of severe adverse reaction associated with any vaccine component

5. Residence in long-term care facility

6. Diagnosis of diabetes (diagnosis of pre-diabetes okay)

7. Chronic renal disease (or eGFR <50 mL/min) or renal failure (defined as receipt of
renal dialysis or transplant) or nephrotic syndrome

8. History of adverse reaction or contraindications associated with metformin

9. Recent history or plan for radiocontrast

10. Self-reported dementia or severe cognitive impairment

11. Receipt of blood products within 6 months before enrollment

12. History of heart disease (New York Heart Classification greater than class II; more
than non-specific ST-T wave changes on the ECG)

13. History of chronic obstructive pulmonary disease

14. Poorly controlled blood pressure (systolic BP>160, diastolic BP>90 mmHg)

15. History of an immunodeficiency

16. Use of use of investigational products, antibiotics, probiotics, or systemic
immunosuppressive therapy (systemic steroids) within 1 month of study start; patients
who are taking these medications chronically, with no expected discontinuation during
the study period would not be considered ineligible.