Vaccination Efficacy With Metformin in Older Adults (VEME)

July 22, 2020 updated by: Jenna Bartley, UConn Health

Vaccination Efficacy With Metformin in Older Adults: A Pilot Study

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
26

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • Farmington, Connecticut, United States, 06030
        • UConn Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

61 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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)).
Drug: 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.
Other Names:
  • metformin ER
  • metformin hydrochloride ER
  • metformin hcl ER
Biological: 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
Other Names:
  • Flu Vaccine
Placebo Comparator: Placebo
Patients will consume 3 identical placebo tablets (after similar 3 week dose gradation).
Biological: 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
Other Names:
  • Flu Vaccine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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
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.
Prior to vaccination (week 12) and 5 weeks post vaccination (week 17)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Influenza Antibody Titers
Time Frame: Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)
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)
Change in T Cell Metabolic Phenotype
Time Frame: Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)
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
Time Frame: Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)
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
Time Frame: Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
UConn Health

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jenna M Bartley, PhD, UConn Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 5, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 4, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 4, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 19, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 20, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 24, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 23, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 22, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 19-205-2
  • 18155 (AFAR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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