Vaccination Efficacy With Metformin in Older Adults

NCT ID: NCT03996538

Last Updated: 2020-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-05
• Study Completion Date: 2020-02-04

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

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)).

Group Type: EXPERIMENTAL

Metformin Hydrochloride Extended-Release Tablets

Intervention Type: 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.

Influenza Vaccine

Intervention Type: BIOLOGICAL

All subjects will be vaccinated with high-dose influenza vaccine at the appropriate time of the year per current CDC and FDA recommendations

Placebo

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

Group Type: PLACEBO_COMPARATOR

Influenza Vaccine

Intervention Type: BIOLOGICAL

All subjects will be vaccinated with high-dose influenza vaccine at the appropriate time of the year per current CDC and FDA recommendations

Interventions

Metformin Hydrochloride Extended-Release Tablets

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.

Intervention Type: DRUG

Influenza Vaccine

All subjects will be vaccinated with high-dose influenza vaccine at the appropriate time of the year per current CDC and FDA recommendations

Intervention Type: BIOLOGICAL

Other Intervention Names

metformin hydrochloride ER; metformin hcl ER; metformin ER; Flu Vaccine

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
• 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)
• Unintentional weight loss >10% in past 12 months
• Allergy or history of adverse reaction to flu vaccine or any ingredients in flu vaccine, including eggs
• History of Guillain-Barre syndrome following vaccination
• Immunosuppressive disorders or taking immunosuppressive medications (including oral prednisone > 10mg/day)
• Current participation in another interventional study
• Refusal to receive flu vaccine

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

UConn Health

OTHER

Sponsor Role: lead

Responsible Party

Jenna Bartley

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jenna M Bartley, PhD

Role: PRINCIPAL_INVESTIGATOR

UConn Health

Locations

UConn Health

Farmington, Connecticut, United States

Countries

United States

Other Identifiers

18155

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

19-205-2

Identifier Type: -

Identifier Source: org_study_id