Clinical trial NCT03996538: Vaccination Efficacy With Metformin in Older Adults
Official title: Vaccination Efficacy With Metformin in Older Adults: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Aging
Age-Related Immunodeficiency
Vaccine Response Impaired
Lead sponsor: UConn Health
Sponsor class: OTHER
First posted: 2019-06-24
Enrollment: 26
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Change in Cell-mediated Flu Vaccine Responses - inducible Granzyme B
timeFrame: Prior to vaccination (week 12) and 5 weeks post vaccination (week 17)
measure: Change in Cell-mediated Flu Vaccine Responses - interferon(IFN)-γ/interleukin(IL)-10 ratio
timeFrame: Prior to vaccination (week 12) and 5 weeks post vaccination (week 17)
Secondary outcomes:
measure: Change in Influenza Antibody Titers
timeFrame: Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)
measure: Change in T Cell Metabolic Phenotype
timeFrame: Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)
measure: Change in T Cell Oxygen Consumption Rate
timeFrame: Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)
measure: Change in Frailty Phenotype
timeFrame: Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22)
Other outcomes:
Locations:
city: Farmington
country: United States
facility: UConn Health
state: Connecticut
Study officials:
affiliation: UConn Health
name: Jenna M Bartley, PhD
role: PRINCIPAL_INVESTIGATOR
References: