Vaccination Efficacy With Metformin in Older Adults

NCT03996538 | Completed Phase 1 FDA Drug

• 2 other identifiers: 19-205-218155
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Aging; Age-Related Immunodeficiency; Vaccine Response Impaired

Outcome Measures

Primary Outcomes (2)

• 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)

Secondary Outcomes (4)

• 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)

Study Arms (2)

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)).

Drug: Metformin Hydrochloride Extended-Release Tablets; Biological: Influenza Vaccine

Placebo

PLACEBO COMPARATOR

Patients will consume 3 identical placebo tablets (after similar 3 week dose gradation).

Biological: Influenza Vaccine

Interventions

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.

Also known as: metformin hydrochloride ER, metformin hcl ER, metformin ER

Metformin Hydrochloride Extended Release Tablets

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

Also known as: Flu Vaccine

Metformin Hydrochloride Extended Release Tablets; Placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Significant co-morbid disease (severe chronic obstructive pulmonary disease, active rheumatologic diseases, chronic infection (HIV, tuberculosis), severe congestive heart failure (NYHA class 4), myocarditis, etc)
• Myocardial infarction, stroke or hospitalization for heart failure in the last 12 months
• Severe active psychiatric disorder (e.g. bipolar, schizophrenia)
• Unable to complete physical performance testing due to medical conditions (at discretion of the PI)
• Uncontrolled hypertension (systolic/diastolic blood pressure \>150/90 mmHg)

Sponsors & Collaborators

• UConn Health: lead

Study Sites (1)

UConn Health

Farmington, Connecticut, 06030, United States

Location

MeSH Terms

Interventions

Metformin; Influenza Vaccines

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Jenna M Bartley, PhD

  UConn Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Metformin and placebo tablets will be identical. Participants and researchers will not know treatment allocation.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 19, 2019
• First Posted: June 24, 2019
• Study Start: June 5, 2019
• Primary Completion: February 4, 2020
• Study Completion: February 4, 2020
• Last Updated: July 23, 2020

Record last verified: 2020-07

Locations

US (1)