Assessment of Metformin for Restoration of Immune Homeostasis in HIV+ and HIV- Individuals With a History of Injection Drug Use ((MET-IH))

April 17, 2026 updated by: Ellen Eaton, University of Alabama at Birmingham

Assessment of Metformin for Restoration of Immune Homeostasis in HIV+ and HIV- Individuals With a History of Injection Drug Use (MET-IH)

This randomized clinical trial (RCT) evaluates whether metformin can reduce systemic inflammation and improve immune function in individuals with a history of injection drug use, with or without HIV. Participants will receive metformin or placebo and undergo immune system assessments, including vaccine response evaluations.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The study aims to assess the impact of metformin on immune dysregulation among 100 adults (ages 18-64) with a history of injection drug use. Participants will be randomized 1:1 to metformin (500mg increasing to 1000mg) or placebo for 16 weeks, during which they will receive Jynneos (MPOX) and Capvaxvie (PCV21, pneumococcal) vaccines. Immunologic responses will be monitored over 6 months post-enrollment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Ellen Eaton, MD, MSPH
  • Phone Number: 205-975-0661
  • Email: eeaton@uabmc.edu

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • University of Alabama at Birmingham
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Provision of signed and dated informed consent.
  • Stated willingness to comply with all study procedures and availability for the study duration.
  • Aged 18 to 64 years old.
  • Weight of at least 110 lbs.
  • Body Mass Index (BMI) of 18.5-40. Enrollment of individuals with BMI >40, deemed in good health, may be considered with approval.
  • Willingness to receive Jynneos (MPOX) and Capvaxvie vaccines.
  • Ability to take oral medication and willingness to adhere to the metformin treatment regimen.
  • History of injection opioid, amphetamine, and/or cocaine use within the past 10 years (self-report).
  • Use of non-prescription opioid, amphetamine, and/or cocaine within the past 30 days (self-report).
  • Clinically confirmed urine drug screen for opioid, amphetamine, and/or cocaine within the past 30 days.
  • Serum CRP > 3 mg/dL.
  • Glucose level between 70-180 mg/dL (non-fasting).
  • Hemoglobin A1c (HbA1c) of 5.0-6.4%.
  • CD4 count > 200 cells/ml.
  • If HIV-positive, HIV viral load < 200 copies/ml.
  • If HIV-positive, on anti-retroviral therapy (ART) for >12 months.

Exclusion Criteria:

  • Inability to give informed consent.
  • Refusal or inability to have blood drawn.
  • Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, platelet disorder requiring precautions).
  • Pregnant or nursing individuals.
  • Diabetes mellitus.
  • History of severe renal impairment or eGFR <60 mL/min/1.73m².
  • Creatinine clearance <60 mL/min.
  • History of liver disease.
  • ALT/AST > 3× the upper limit of normal.
  • Total bilirubin >1.4 mg/dL.
  • Albumin <3.5 g/dL.
  • Prothrombin >1.5× the upper limit of normal.
  • AUDIT-C score ≥8.
  • Hemoglobin <9.0 g/L.
  • Absolute neutrophil count <1,000/mL.
  • Platelet count <100,000/mL.
  • History of acute or chronic metabolic acidosis.
  • Serum bicarbonate <22 mEq/L.
  • Anion gap >10 mEq/L.
  • Serum lactate >2.2 mmol/L.
  • Serum vitamin B12 <250 pg/mL.
  • History of chronic diarrhea.
  • Current use of metformin or other diabetes medications.
  • History of myocardial infarction, endocarditis, stroke, heart failure, chronic obstructive pulmonary disease, or sepsis.
  • Use of medications such as furosemide, nifedipine, ranolazine, vandetanib, or cimetidine (current or within the past 30 days).
  • Active hepatitis B infection.
  • Hepatitis C infection within 6 months of study entry; individuals with prior hepatitis C must be at least 6 months post-treatment with direct-acting antivirals.
  • Previous receipt of Jynneos or pneumococcal vaccine within the past two years (self-report).
  • Severe allergic reaction to metformin, Jynneos, or Capvaxvie (self-report). Blood donations exceeding 450 mL in the 8 weeks prior to enrollment, accounting for study-related blood draws.
  • Any medical, psychiatric, social condition, or responsibility that, in the investigator's judgment, could interfere with study procedures.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Metformin Group
Participants will receive Metformin ER (500mg increasing to 1000mg) for 16 weeks to assess immune restoration and inflammatory response.
Drug: Metformin
Participants will receive Metformin ER (500mg increasing to 1000mg) or placebo for 16 weeks to assess immune restoration and inflammatory response.
Biological: Jynneos
All participants will take a Jynneos (MPOX) vaccine.
Biological: Capvaxvie
All participants will take a Capvaxvie (PCV21, pneumococcal) vaccine.
Placebo Comparator: Placebo Group
Control Group
Biological: Jynneos
All participants will take a Jynneos (MPOX) vaccine.
Biological: Capvaxvie
All participants will take a Capvaxvie (PCV21, pneumococcal) vaccine.
Drug: Placebo
Participants will receive placebo for 16 weeks and assess immune restoration and inflammatory response.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Serum C-reactive Protein (CRP)
Time Frame: Baseline to Week 16
Assessed by Enzyme Linked Immunosorbent Assay (ELISA) of blood samples collected at baseline and at 16 weeks. Reported in mg/dL.
Baseline to Week 16

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in exhausted B cells
Time Frame: Baseline to Week 16
Assessed by flow cytometry of blood samples collected at baseline and at 16 weeks. Reported as percentage of total B cells.
Baseline to Week 16
Change in exhausted T cells
Time Frame: Baseline to Week 16
Assessed by flow cytometry of blood samples collected at baseline and at 16 weeks. Reported as percentage of total T cells.
Baseline to Week 16
Change in MPOX vaccine-specific IgG antibody.
Time Frame: Baseline to Week 13
Assessed by Enzyme Linked Immunosorbent Assay (ELISA) of blood samples collected at baseline and at 13 weeks. Reported as micrograms/mL.
Baseline to Week 13
Change in PCV21 vaccine-specific IgG antibody.
Time Frame: Baseline to Week 9
Assessed by Enzyme Linked Immunosorbent Assay (ELISA) of blood samples collected at baseline and at 9 weeks. Reported as micrograms/mL.
Baseline to Week 9

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Alabama at Birmingham

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Drug Abuse (NIDA)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 7, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 4, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 10, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 17, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 17, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 000543853
  • 1R01DA060692-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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