Vaccination Efficacy With Metformin in Older Adults: A Pilot Study
Overview
- Phase
- Phase 1
- Intervention
- Metformin Hydrochloride Extended-Release Tablets
- Conditions
- Aging
- Sponsor
- UConn Health
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Change in Cell-mediated Flu Vaccine Responses - inducible Granzyme B
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Investigators
Jenna Bartley
Assistant Professor
UConn Health
Eligibility Criteria
Inclusion Criteria
- •Men and women 65 years and older
- •Willingness to provide consent and participate in all aspects of the trial including randomization to the intervention group and receiving this year's flu vaccine
- •Received previous year's seasonal influenza vaccine
Exclusion Criteria
- •History of severe renal impairment and/or eGFR ≤ 45 mL/min/1.73m2
- •Excessive alcohol use (more than 14 alcoholic drinks/week) or clinical/laboratory evidence of hepatic disease (via medical history and/or AST and/or ALT ≥ 3 times upper limit of normal at screening)
- •Acute or chronic metabolic acidosis (via medical history and/or low serum bicarbonate (\< 22mEq/L), increased anion gap (\> 10 mEq/L))
- •History of B12 deficiency within the last 10 years
- •Known type 2 diabetes or screening of prediabetic (HbA1c 5.7-6.4%) or diabetic (HbA1c ≥ 6.5%)
- •Currently taking metformin or other diabetes medications
- •Unwilling or unable (due to significant cognitive impairment) to provide informed consent
- •Terminal illness with life expectancy less than 12 months
- •Advanced neurological disorder (Parkinson's, ALS, MS, dementia)
- •Cancer or history of cancer in the past 2 years (excluding non-melanoma skin cancer) or any history of metastatic (stage 4) cancer
Arms & Interventions
Metformin Hydrochloride Extended Release Tablets
Patients will consume 3 tablets of 500mg metformin hydrochloride extended-release tablets daily (1500mg/day (after 3 week dose gradation)).
Intervention: Metformin Hydrochloride Extended-Release Tablets
Metformin Hydrochloride Extended Release Tablets
Patients will consume 3 tablets of 500mg metformin hydrochloride extended-release tablets daily (1500mg/day (after 3 week dose gradation)).
Intervention: Influenza Vaccine
Placebo
Patients will consume 3 identical placebo tablets (after similar 3 week dose gradation).
Intervention: Influenza Vaccine
Outcomes
Primary Outcomes
Change in Cell-mediated Flu Vaccine Responses - inducible Granzyme B
Time Frame: Prior to vaccination (week 12) and 5 weeks post vaccination (week 17)
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.
Change in Cell-mediated Flu Vaccine Responses - interferon(IFN)-γ/interleukin(IL)-10 ratio
Time Frame: Prior to vaccination (week 12) and 5 weeks post vaccination (week 17)
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.
Secondary Outcomes
- Change in Influenza Antibody Titers(Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22))
- Change in T Cell Metabolic Phenotype(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(Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22))
- Change in Frailty Phenotype(Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22))