AgingPhase 1VEMENCT03996538
Vaccination Efficacy With Metformin in Older Adults
A Phase 1 study testing Metformin Hydrochloride Extended-Release Tablets and Influenza Vaccine in people with Aging and Age-Related Immunodeficiency, run by UConn Health at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 65 years and olderHealthy volunteers can take part
- Conditions the study is for
- Aging, Age-Related Immunodeficiency, Vaccine Response Impaired
- What is being tested?
- Metformin Hydrochloride Extended-Release Tablets and Influenza Vaccine
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jun 2019to 4 Feb 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Being tested
- Metformin Hydrochloride Extended-Release Tablets, Influenza Vaccine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin Hydrochloride Extended-Release TabletsDrug
Also called metformin hydrochloride ER, metformin hcl ER, metformin ER
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 VaccineBiological
Also called Flu Vaccine
All subjects will be vaccinated with high-dose influenza vaccine at the appropriate time of the year per current CDC and FDA recommendations
| Study group | Role | What they receive |
|---|---|---|
| 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)). Receives: 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). Receives: Biological: Influenza Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Prior to vaccination (week 12) and 5 weeks post vaccination (week 17)
Secondary outcomes (4)
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.
Measured: Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)
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.
Measured: 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
T cells will be evaluated for oxygen consumption rate via Seahorse Agilent Technologies. Change in oxygen consumption rate over time will be evaluated.
Measured: Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)
Change in Frailty Phenotype
Subjects will complete frailty testing via Fried Frailty Phenotype. Change in frailty phenotype over time will be evaluated.
Measured: Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2019
- Study start5 Jun 2019
- Primary completion4 Feb 2020
- Study completion4 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AgingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- UConn Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jenna Bartley, UConn Health
- Investigators
- Jenna M Bartley, PhD, Principal investigator, UConn Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03996538
- Sponsor's protocol ID
- 19-205-2
- Other IDs
- 18155
- Acronym
- VEME
- Status last verified
- Jul 2020
- First submitted
- 19 Jun 2019
- Last updated
- 23 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vaccination Efficacy With Metformin in Older Adults: A Pilot Study
- ClinicalTrials.gov ID
- NCT03996538
- Acronym / sponsor ID
- VEME / 19-205-2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- UConn HealthUniversity, hospital or other
- Study start
- 5 Jun 2019 (actual)
- Primary completion
- 4 Feb 2020 (actual)
- Study completion
- 4 Feb 2020 (actual)
- First posted
- 24 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin Hydrochloride Extended Release Tablets | Experimental | Drug: Metformin Hydrochloride Extended-Release Tablets, Biological: Influenza VaccinePatients will consume 3 tablets of 500mg metformin hydrochloride extended-release tablets daily (1500mg/day (after 3 week dose gradation)). |
| Placebo | Placebo comparator | Biological: Influenza VaccinePatients will consume 3 identical placebo tablets (after similar 3 week dose gradation). |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (21 listed)
- 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%)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin Hydrochloride Extended-Release TabletsAlso: metformin hydrochloride ER, metformin hcl ER, metformin ERSubjects 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. | Drug | Metformin Hydrochloride Extended Release Tablets |
| Influenza VaccineAlso: Flu VaccineAll subjects will be vaccinated with high-dose influenza vaccine at the appropriate time of the year per current CDC and FDA recommendations | Biological | Metformin Hydrochloride Extended Release Tablets, Placebo |
Primary outcome
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.
4 secondary outcomes
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)
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)
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)
Change in Frailty Phenotype
Time frame: Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jenna M Bartley, PhD principal investigator
UConn Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Metformin Hydrochloride Extended-Release Tablets and Influenza Vaccine in people with Aging and Age-Related Immunodeficiency, run by UConn Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cell-mediated Flu Vaccine Responses - inducible Granzyme B (time frame: Prior to vaccination (week 12) and 5 weeks post vaccination (week 17)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2020.