Impact of Metformin on Immunity

NCT ID: NCT03713801

Last Updated: 2024-08-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-14
• Study Completion Date: 2024-07-16

Brief Summary

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

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.

Conditions

Aging; Vaccine Response Impaired

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

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 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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Glucophage; Placebo oral tablet

Eligibility Criteria

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

• Minimum Eligible Age: 63 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Grace Lee, PhD

Role: PRINCIPAL_INVESTIGATOR

UT Health San Antonio

Locations

UT Health San Antonio

San Antonio, Texas, United States

Countries

United States

Other Identifiers

20180171H

Identifier Type: -

Identifier Source: org_study_id