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Vaccination Efficacy With Metformin in Older Adults (VEME)

Primary Purpose

Aging, Age-Related Immunodeficiency, Vaccine Response Impaired

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Metformin Hydrochloride Extended-Release Tablets

Influenza Vaccine

About this trial

This is an interventional basic science trial for Aging

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

UConn Health

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Metformin Hydrochloride Extended Release Tablets

Placebo

Arm Description

Patients will consume 3 tablets of 500mg metformin hydrochloride extended-release tablets daily (1500mg/day (after 3 week dose gradation)).

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

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

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.

Change in Frailty Phenotype

Subjects will complete frailty testing via Fried Frailty Phenotype. Change in frailty phenotype over time will be evaluated.

Full Information

NCT ID

NCT03996538

First Posted

June 19, 2019

Last Updated

July 22, 2020

Sponsor

UConn Health

1. Study Identification

Unique Protocol Identification Number

NCT03996538

Brief Title

Vaccination Efficacy With Metformin in Older Adults

Acronym

VEME

Official Title

Vaccination Efficacy With Metformin in Older Adults: A Pilot Study

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

June 5, 2019 (Actual)

Primary Completion Date

February 4, 2020 (Actual)

Study Completion Date

February 4, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

UConn Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Aging, Age-Related Immunodeficiency, Vaccine Response Impaired

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Masking Description

Metformin and placebo tablets will be identical. Participants and researchers will not know treatment allocation.

Allocation

Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Metformin Hydrochloride Extended Release Tablets

Arm Type

Experimental

Arm Description

Patients will consume 3 tablets of 500mg metformin hydrochloride extended-release tablets daily (1500mg/day (after 3 week dose gradation)).

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Metformin Hydrochloride Extended-Release Tablets

Other Intervention Name(s)

metformin hydrochloride ER, metformin hcl ER, metformin ER

Intervention Description

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

Biological

Intervention Name(s)

Influenza Vaccine

Other Intervention Name(s)

Flu Vaccine

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in Cell-mediated Flu Vaccine Responses - inducible Granzyme B

Description

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.

Time Frame

Prior to vaccination (week 12) and 5 weeks post vaccination (week 17)

Title

Change in Cell-mediated Flu Vaccine Responses - interferon(IFN)-γ/interleukin(IL)-10 ratio

Description

Time Frame

Prior to vaccination (week 12) and 5 weeks post vaccination (week 17)

Secondary Outcome Measure Information:

Title

Change in Influenza Antibody Titers

Description

Time Frame

Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)

Title

Change in T Cell Metabolic Phenotype

Description

Time Frame

Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)

Title

Change in T Cell Oxygen Consumption Rate

Description

T cells will be evaluated for oxygen consumption rate via Seahorse Agilent Technologies. Change in oxygen consumption rate over time will be evaluated.

Time Frame

Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)

Title

Change in Frailty Phenotype

Description

Subjects will complete frailty testing via Fried Frailty Phenotype. Change in frailty phenotype over time will be evaluated.

Time Frame

Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jenna M Bartley, PhD

Organizational Affiliation

UConn Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

UConn Health

City

Farmington

State/Province

Connecticut

ZIP/Postal Code

06030

Country

United States

12. IPD Sharing Statement

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Vaccination Efficacy With Metformin in Older Adults

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