Impact of Metformin on Immunity

Aging Clinical Trial

Official title:

Metformin and Vaccine Response in Older Adults

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT03713801
• Other study ID #: 20180171H
• Status: Suspended
• Phase: Phase 1
• Start date: January 14, 2019
• Est. completion date: July 2026

Study information

• Verified date: August 2023
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 18
• Est. completion date: July 2026
• Est. primary completion date: July 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 63 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Aging
• Vaccine Response Impaired

Intervention

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.
• 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

Locations

Country	Name	City	State
United States	UT Health San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in antibody responses to PCV13	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.	Change from 4 weeks to 8 weeks
Secondary	Measure of immunophenotypes	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.	Baseline, 4 weeks and 8 weeks