Impact of Metformin on Immunity

Sponsor
The University of Texas Health Science Center at San Antonio (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03713801
Collaborator
(none)
18
1
2
47.5
0.4

Study Details

Study Description

Brief Summary

To determine whether metformin (MET) can improve the immune response to the pneumococcal conjugate vaccine (PCV-13) in older adults.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

The objective of this study is to determine whether metformin (MET) can improve the immune response to the pneumococcal conjugate vaccine (PCV-13) in older adults, and if this effect is mediated by the gut microbiota.

The proposed research projects will provide the necessary pilot data for future, more definitive, studies that will evaluate the impact of immunomodulatory therapies, such as MET therapy, on the aging immune system. The specific aims are:

Aim 1. Compare PCV13 vaccine response in elderly adults (≥63 years of age) treated with MET vs. placebo. For this study, 50 elderly volunteers will be enrolled and randomly assigned to receive MET or placebo. The hypothesis that MET can improve vaccine responsiveness by measuring serotype-specific IgG concentrations before and 30 days after PCV13 administration will be tested.

Aim 2. Determine whether the frequencies of immunophenotypes differ between elderly adults treated with MET vs. placebo. The mechanisms of MET's effect on the immune system by comparing immunophenotypes of MET and placebo groups between baseline and prior to PCV13 and between baseline and 30 days after PCV13 administration will be explored.

Study Design

Study Type:
Interventional
Actual Enrollment :
18 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Basic Science
Official Title:
Metformin and Vaccine Response in Older Adults
Actual Study Start Date :
Jan 14, 2019
Actual Primary Completion Date :
Jul 4, 2020
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Metformin

Dosage is increased over the first 3 weeks up to three 500 mg tablets a day at 3 weeks, then continued on 3 tablets daily for a further 9 weeks.

Drug: Metformin
Total daily dose titrated up to 1500 mg po q day over the course of 3 weeks and continued for a total exposure of 12 weeks.
Other Names:
  • Glucophage
  • Placebo Comparator: Placebo

    Placebo tablet dosage is increased over the first 3 weeks up to three tablets a day at 3 weeks, then continued on 3 tablets daily for a further 9 weeks.

    Drug: Placebo
    Placebo tablets titrated up to 3 tablets over the course of 3 weeks and then continued as 3 daily for a total exposure of 12 weeks
    Other Names:
  • Placebo oral tablet
  • Outcome Measures

    Primary Outcome Measures

    1. Change in antibody responses to PCV13 [Change from 4 weeks to 8 weeks]

      The primary outcome will be antibody responses to PCV13. Antibody levels of each of the 13 different serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) will be compared between the pre-treatment values and the post treatment values.

    Secondary Outcome Measures

    1. Measure of immunophenotypes [Baseline, 4 weeks and 8 weeks]

      The distribution of immunophenotypes will be presented descriptively at each time point for each treatment group. To determine which immunophenotypes differed between MET and placebo groups, changes will be determined using within-patient cell count ratios for each measured phenotype between baseline and 6-weeks of study drug treatment and between baseline and the 30 days after PCV13.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    63 Years to 90 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    1. Age 63 to 89 years of age

    2. No history of pneumococcal vaccinations

    3. Able to take oral medications

    4. Able to provide informed consent

    5. Not currently taking metformin

    Exclusion Criteria:
    1. Previous vaccination with any pneumococcal vaccine

    2. Metformin within the last 6 months

    3. Contraindication for PCV13

    4. History of severe adverse reaction associated with any vaccine component

    5. Residence in long-term care facility

    6. Diagnosis of diabetes (diagnosis of pre-diabetes okay)

    7. Chronic renal disease (or eGFR <50 mL/min) or renal failure (defined as receipt of renal dialysis or transplant) or nephrotic syndrome

    8. History of adverse reaction or contraindications associated with metformin

    9. Recent history or plan for radiocontrast

    10. Self-reported dementia or severe cognitive impairment

    11. Receipt of blood products within 6 months before enrollment

    12. History of heart disease (New York Heart Classification greater than class II; more than non-specific ST-T wave changes on the ECG)

    13. History of chronic obstructive pulmonary disease

    14. Poorly controlled blood pressure (systolic BP>160, diastolic BP>90 mmHg)

    15. History of an immunodeficiency

    16. Use of use of investigational products, antibiotics, probiotics, or systemic immunosuppressive therapy (systemic steroids) within 1 month of study start; patients who are taking these medications chronically, with no expected discontinuation during the study period would not be considered ineligible.

    17. Treatment with anticoagulants (warfarin)

    18. Donated blood within the last 2 months

    19. Subject is considered unsuitable for the study in the opinion of the investigator for any other reason

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UT Health San Antonio San Antonio Texas United States 78229

    Sponsors and Collaborators

    • The University of Texas Health Science Center at San Antonio

    Investigators

    • Principal Investigator: Grace Lee, PhD, UT Health San Antonio

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    The University of Texas Health Science Center at San Antonio
    ClinicalTrials.gov Identifier:
    NCT03713801
    Other Study ID Numbers:
    • 20180171H
    First Posted:
    Oct 22, 2018
    Last Update Posted:
    Feb 8, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 8, 2022