Systemic InflammationPhase 4(MET-IH)NCT06829238
Assessment of Metformin for Restoration of Immune Homeostasis in HIV+ and HIV- Individuals With a History of Injection Drug Use
A Phase 4 study testing Metformin, Jynneos and Capvaxvie in people with Systemic Inflammation and Immune Dysregulation, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Systemic Inflammation, Immune Dysregulation, Injection Drug Use
- What is being tested?
- Metformin, Jynneos and Capvaxvie
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Apr 2025to 30 Nov 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Show all 16Show fewer
- 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.
Who cannot join
- 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.
Show all 30Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Ellen Eaton, MD, MSPH, 205-975-0661, eeaton@uabmc.edu
James Kobie, PhD, jjkobie@uabmc.edu
About this study
Official title: 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.
Read the 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.
- Conditions
- Systemic Inflammation, Immune Dysregulation, Injection Drug Use, HIV
- Being tested
- Metformin, Placebo, Jynneos, Capvaxvie
- Keywords
- Metformin, Immune restoration, Vaccine response, People who inject drugs (PWID)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Participants will receive Metformin ER (500mg increasing to 1000mg) or placebo for 16 weeks to assess immune restoration and inflammatory response.
PlaceboDrug
Participants will receive placebo for 16 weeks and assess immune restoration and inflammatory response.
JynneosBiological
All participants will take a Jynneos (MPOX) vaccine.
CapvaxvieBiological
All participants will take a Capvaxvie (PCV21, pneumococcal) vaccine.
| Study group | Role | What they receive |
|---|---|---|
| Metformin Group | Experimental | Participants will receive Metformin ER (500mg increasing to 1000mg) for 16 weeks to assess immune restoration and inflammatory response. Receives: Drug: Metformin; Biological: Jynneos; Biological: Capvaxvie |
| Placebo Group | Placebo comparator | Control Group Receives: Drug: Placebo; Biological: Jynneos; Biological: Capvaxvie |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Serum C-reactive Protein (CRP)
Assessed by Enzyme Linked Immunosorbent Assay (ELISA) of blood samples collected at baseline and at 16 weeks. Reported in mg/dL.
Measured: Baseline to Week 16
Secondary outcomes (4)
Change in exhausted B cells
Assessed by flow cytometry of blood samples collected at baseline and at 16 weeks. Reported as percentage of total B cells.
Measured: Baseline to Week 16
Change in exhausted T cells
Assessed by flow cytometry of blood samples collected at baseline and at 16 weeks. Reported as percentage of total T cells.
Measured: Baseline to Week 16
Change in MPOX vaccine-specific IgG antibody.
Assessed by Enzyme Linked Immunosorbent Assay (ELISA) of blood samples collected at baseline and at 13 weeks. Reported as micrograms/mL.
Measured: Baseline to Week 13
Change in PCV21 vaccine-specific IgG antibody.
Assessed by Enzyme Linked Immunosorbent Assay (ELISA) of blood samples collected at baseline and at 9 weeks. Reported as micrograms/mL.
Measured: Baseline to Week 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2025
- Study start7 Apr 2025
- Primary completion30 Nov 2028 (estimated)
- Study completion30 Nov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic InflammationStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Ellen Eaton, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06829238
- Sponsor's protocol ID
- 000543853
- Other IDs
- 1R01DA060692-01A1
- Acronym
- (MET-IH)
- Status last verified
- Apr 2026
- First submitted
- 4 Feb 2025
- Last updated
- 22 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Metformin for Restoration of Immune Homeostasis in HIV+ and HIV- Individuals With a History of Injection Drug Use (MET-IH)
- ClinicalTrials.gov ID
- NCT06829238
- Acronym / sponsor ID
- (MET-IH) / 000543853
- Conditions
- Systemic Inflammation, Immune Dysregulation, Injection Drug Use, HIV
- Keywords
- Metformin, Immune restoration, Vaccine response, People who inject drugs (PWID)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 7 Apr 2025 (actual)
- Primary completion
- 30 Nov 2028 (estimated)
- Study completion
- 30 Nov 2029 (estimated)
- First posted
- 17 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin Group | Experimental | Drug: Metformin, Biological: Jynneos, Biological: CapvaxvieParticipants will receive Metformin ER (500mg increasing to 1000mg) for 16 weeks to assess immune restoration and inflammatory response. |
| Placebo Group | Placebo comparator | Drug: Placebo, Biological: Jynneos, Biological: CapvaxvieControl Group |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (30 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminParticipants will receive Metformin ER (500mg increasing to 1000mg) or placebo for 16 weeks to assess immune restoration and inflammatory response. | Drug | Metformin Group |
| PlaceboParticipants will receive placebo for 16 weeks and assess immune restoration and inflammatory response. | Drug | Placebo Group |
| JynneosAll participants will take a Jynneos (MPOX) vaccine. | Biological | Metformin Group, Placebo Group |
| CapvaxvieAll participants will take a Capvaxvie (PCV21, pneumococcal) vaccine. | Biological | Metformin Group, Placebo Group |
Primary outcome
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.
4 secondary outcomes
Change in exhausted B cells
Time frame: Baseline to Week 16
Change in exhausted T cells
Time frame: Baseline to Week 16
Change in MPOX vaccine-specific IgG antibody.
Time frame: Baseline to Week 13
Change in PCV21 vaccine-specific IgG antibody.
Time frame: Baseline to Week 9
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Systemic Inflammation
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
Infection, Sepsis
Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin, Jynneos and Capvaxvie in people with Systemic Inflammation and Immune Dysregulation, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ellen Eaton, MD, MSPH (205-975-0661, eeaton@uabmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Serum C-reactive Protein (CRP) (time frame: Baseline to Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2026.