HIV/AIDSPhase 2/3NCT04500678
Impact of Metformin on Immuno-virologic Parameters in HIV
A Phase 2/3 study testing Metformin in people with HIV/AIDS, run by University of Hawaii at 1 site in United States.
Trial summary
Non-diabetic, aviremic HIV-infected individuals on antiretroviral therapy (ART) will be randomized to metformin therapy or to observation for 72 weeks. Primary objective is to assess change over 72 weeks in CD4 T cell negative checkpoint receptors (PD-1 and TIGIT). Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- HIV/AIDS
- What is being tested?
- Metformin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2019to 31 Dec 2022
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV+
- On suppressive ART stable for > 1 year
- Plasma HIV RNA < 50 copies/mL within 3 months of entry, with no HIV RNA > 200 copies/mL within the past 6 months prior to entry
- Age >40 years
- Ability and willingness to provide written informed consent
Who cannot join
- Uncontrolled chronic medical condition or cancer
- Acute illness within 2 weeks of entry
- Diagnosis of diabetes by history, fasting blood glucose >126, or by HgbA1c > 6.5
- Chronic, uncontrolled diarrhea
- Known hypersensitivity or contraindication to metformin use
- Current presence of hepatitis C including currently on or intent to start therapy for hepatitis C within the 48 week duration of study.
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- Serum B12 level below the reference normal range as listed by the commercial lab utilized for this study (Diagnostic Laboratory Services)
- Pregnancy, or intent to become pregnant or nursing an infant
- Any immunomodulator, HIV vaccine, any other vaccine, or investigational therapy within 30 days of study entry.
- Current uncontrolled coronary artery disease or NYHA Class 3 or 4 congestive heart failure
- History of liver cirrhosis
- Current use of zidovudine, stavudine or didanosine
- The following lab values
- Hemoglobin < 9.0 g/dL
- Absolute neutrophil count < 1000/μL
- Platelet count < 50,000/μL
- AST (SGOT) and ALT (SGPT) > 5x upper limit of normal (ULN)
- Calculated creatinine clearance (Cockcroft and Gault) < 50 ml/min
- Active or recent past history (within past 2 years) of illicit substance or alcohol use or abuse which, in the judgment of the Investigator, will interfere with the patient's ability to comply with the protocol requirements
- Patients, who, in the opinion of the Investigator, are unable to comply with the dosing schedule and protocol evaluation or for whom the study may not be advisable
Trial locations and contacts
1 site in 1 country.
United States1 site
John A. Burns School of Medicine, University of Hawaii - Manoa
Honolulu, Hawaii, 96813
About this study
Official title: A 72 Week, Randomized, Open-label vs Observation Study to Assess the Potential Immuno-virologic Benefit of Metformin in HIV-infected Individuals Receiving Antiretroviral Therapy
Non-diabetic, aviremic HIV-infected individuals on antiretroviral therapy (ART) will be randomized to metformin therapy or to observation for 72 weeks. Primary objective is to assess change over 72 weeks in CD4 T cell negative checkpoint receptors (PD-1 and TIGIT). The study will also explore the 72 week impact of metformin on change in carotid intima-media thickness (cIMT) as a surrogate marker of atherosclerosis, on neuropsychological (NP) performance, strength, and change in body composition.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Metformin 500 mg Extended Release (ER) qd increasing to 1000 mg ER qd at week 4 and continued to week 48.
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | Metformin 500 mg Extended Release (ER) qd increasing to 1000 mg ER qd at week 4 and continued to week 48. Receives: Drug: Metformin |
| Observation | No intervention | Observed without metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Percentage of CD4 T Cells Expressing PD1+TIGIT+
Percentage of CD4 T cells co-expressing PD-1 and TIGIT. Change calculated as Week 72 minus Entry; negative values indicate a decrease.
Measured: Entry to week 72
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2020
- Study start1 Feb 2019
- Primary completion1 Feb 2022
- Study completion31 Dec 2022
Why it stopped: During the COVID pandemic, our IRB halted enrollment into the study among other changes. Post COVID it was decided that too long an interval between patient enrollment was problematic for the study and a discussion was made to terminate.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV/AIDSStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Metformin vs Observation
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Hawaii
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Cecilia M Shikuma, University of Hawaii
- Investigators
- Cecilia M Shikuma, MD, Principal investigator, University of Hawaii
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04500678
- Sponsor's protocol ID
- H046
- Status last verified
- Jul 2025
- First submitted
- 31 Jul 2020
- Last updated
- 20 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Dataset will be available to other researchers upon request once the primary manuscript is written
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 72 Week, Randomized, Open-label vs Observation Study to Assess the Potential Immuno-virologic Benefit of Metformin in HIV-infected Individuals Receiving Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT04500678
- Acronym / sponsor ID
- H046
- Conditions
- HIV/AIDS
- Keywords
- HIV, metformin
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: During the COVID pandemic, our IRB halted enrollment into the study among other changes. Post COVID it was decided that too long an interval between patient enrollment was problematic for the study and a discussion was made to terminate.
- Enrolment
- 29 participants (actual)
- Lead sponsor
- University of HawaiiUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 1 Feb 2019 (actual)
- Primary completion
- 1 Feb 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 5 Aug 2020 (actual)
- Results
- Posted 20 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Non-diabetic, aviremic HIV-infected individuals on antiretroviral therapy (ART) will be randomized to metformin therapy or to observation for 72 weeks. Primary objective is to assess change over 72 weeks in CD4 T cell negative checkpoint receptors (PD-1 and TIGIT). The study will also explore the 72 week impact of metformin on change in carotid intima-media thickness (cIMT) as a surrogate marker of atherosclerosis, on neuropsychological (NP) performance, strength, and change in body composition.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Metformin vs Observation
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: MetforminMetformin 500 mg Extended Release (ER) qd increasing to 1000 mg ER qd at week 4 and continued to week 48. |
| Observation | No intervention | –Observed without metformin |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- HIV+
- On suppressive ART stable for > 1 year
- Plasma HIV RNA < 50 copies/mL within 3 months of entry, with no HIV RNA > 200 copies/mL within the past 6 months prior to entry
- Age >40 years
- Ability and willingness to provide written informed consent
Key exclusion criteria (20 listed)
- Uncontrolled chronic medical condition or cancer
- Acute illness within 2 weeks of entry
- Diagnosis of diabetes by history, fasting blood glucose >126, or by HgbA1c > 6.5
- Chronic, uncontrolled diarrhea
- Known hypersensitivity or contraindication to metformin use
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 |
|---|---|---|
| MetforminMetformin 500 mg Extended Release (ER) qd increasing to 1000 mg ER qd at week 4 and continued to week 48. | Drug | Metformin |
Primary outcome
Change in Percentage of CD4 T Cells Expressing PD1+TIGIT+
Time frame: Entry to week 72
Percentage of CD4 T cells co-expressing PD-1 and TIGIT. Change calculated as Week 72 minus Entry; negative values indicate a decrease.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Dataset will be available to other researchers upon request once the primary manuscript is written
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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. This study is not recruiting at the moment.
Cecilia M Shikuma, MD principal investigator
University of Hawaii
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Metformin in people with HIV/AIDS, run by University of Hawaii 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 5 inclusion and 20 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: stopped early, as of the sponsor's last update on 20 Oct 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Percentage of CD4 T Cells Expressing PD1+TIGIT+ (time frame: Entry to week 72). 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 20 Oct 2026.