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| ID | Type | Description | Link |
|---|---|---|---|
| 18155 | Other Grant/Funding Number | AFAR |
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With aging the immune system gets weaker. This makes older adults more susceptible to influenza (flu). Vaccinations help to prevent infection from the flu virus, however the immune system of older adults do not respond as well to vaccines compared to young adults and thus, aren't as well protected from the complications from the flu. This research is being done to determine if Metformin, an FDA-approved diabetes medication, is effective at enhancing immune responses to flu vaccine in older men and women. Participants will be randomly assigned to either metformin or placebo treatment for a total of 22 weeks. Participants will be vaccinated with high-dose flu vaccine after 12 weeks of treatment. Immune responses will be evaluated throughout the study at 6 time points.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin Hydrochloride Extended Release Tablets | Experimental | Patients will consume 3 tablets of 500mg metformin hydrochloride extended-release tablets daily (1500mg/day (after 3 week dose gradation)). |
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| Placebo | Placebo Comparator | Patients will consume 3 identical placebo tablets (after similar 3 week dose gradation). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin Hydrochloride Extended-Release Tablets | Drug | Subjects will ingest 1500mg/day of metformin hydrochloride extended release. Immune responses will be examined prior to treatment, prior to flu vaccination, and after flu vaccination. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Cell-mediated Flu Vaccine Responses - inducible Granzyme B | Change in inducible Granzyme B levels in peripheral blood mononuclear cells (PBMCs) stimulated ex vivo with live flu virus will be compared between the metformin and placebo group. | Prior to vaccination (week 12) and 5 weeks post vaccination (week 17) |
| Change in Cell-mediated Flu Vaccine Responses - interferon(IFN)-γ/interleukin(IL)-10 ratio | Change in interferon(IFN)-γ/interleukin(IL)-10 ratio in culture supernatant of peripheral blood mononuclear cells (PBMCs) stimulated ex vivo with live flu virus will be compared between the metformin and placebo group. | Prior to vaccination (week 12) and 5 weeks post vaccination (week 17) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Influenza Antibody Titers | Serum antibody titers will be analyzed via hemagglutination inhibition assays (HI) via established Center for Disease Control (CDC) and World Health Organization (WHO) protocols for each vaccine strain. Change in antibody titer levels over time will be evaluated. | Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jenna M Bartley, PhD | UConn Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UConn Health | Farmington | Connecticut | 06030 | United States |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| D007252 | Influenza Vaccines |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D014765 |
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Metformin and placebo tablets will be identical. Participants and researchers will not know treatment allocation.
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| Influenza Vaccine | Biological | All subjects will be vaccinated with high-dose influenza vaccine at the appropriate time of the year per current CDC and FDA recommendations |
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| Change in T Cell Metabolic Phenotype | T cells will be evaluated for phenotypic differences of glucose transporter expression via flow cytometry and reported as percent positive cells. Change in percent positive cells over time will be evaluated. | Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22) |
| Change in T Cell Oxygen Consumption Rate | T cells will be evaluated for oxygen consumption rate via Seahorse Agilent Technologies. Change in oxygen consumption rate over time will be evaluated. | Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22) |
| Change in Frailty Phenotype | Subjects will complete frailty testing via Fried Frailty Phenotype. Change in frailty phenotype over time will be evaluated. | Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22) |
| Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |