Clinical trial NCT03713801: Impact of Metformin on Immunity
Official title: Metformin and Vaccine Response in Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Aging
Vaccine Response Impaired
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
First posted: 2018-10-22
Enrollment: 18
Sex: ALL
Minimum age (years): 63
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Change in antibody responses to PCV13
timeFrame: Change from 4 weeks to 8 weeks
Secondary outcomes:
measure: Measure of immunophenotypes
timeFrame: Baseline, 4 weeks and 8 weeks
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
Study officials:
affiliation: UT Health San Antonio
name: Grace Lee, PhD
role: PRINCIPAL_INVESTIGATOR
References: