Oral Metformin for Treatment of ABCA4 Retinopathy

Oral Metformin for Treatment of ABCA4 Retinopathy (NCT04545736) is a Phase 1 / Phase 2 interventional studying ABCA4 Retinopathy and Stargardt Disease, sponsored by National Eye Institute (NEI). RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

Background: ABCA4 retinopathy is a genetic disease in which the ABCA4 protein is absent or faulty. It can cause waste material to collect in the eye and may cause cells to die. The cell death can lead to vision loss. Researchers want to see if an oral drug called metformin can help. Objective: To see if metformin is safe and possibly helps to slow the rate of ABCA4 retinopathy. Eligibility: People age 12 and older who have ABCA4 retinopathy and have problems with their vision. Design: Participants will be screened under a separate protocol. Participants will have a medical and family history. They will complete a questionnaire about their vision and daily activities. They will have a physical exam. They may have blood drawn through a needle in the arm. Participants will have an eye exam. Their pupils may be dilated with eye drops. Their retina may be photographed. Participants will have a visual field test. They will sit in front of a large dome and press a button when they see a light within the dome. Participants will have an electroretinogram. It examines the function of the retina. They will sit in the dark for 30 minutes. Then their eyes will be numbed with eye drops. They will wear contact lenses that can sense signals from the retinas. They will watch flashing lights. Participants will have optical coherence tomography. This non-invasive procedure makes pictures of the retina. Participants will have fundus autofluorescence. A bright blue light will be shone into their eye. Participants will take metformin by mouth for 24 months. Participants will have study visits every 6 months. Participation will last for at least 36 months....

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For ABCA4 Retinopathy, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 56 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused ABCA4 Retinopathy subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

* Who May Qualify: To be eligible, the following inclusion criteria must be met, where applicable. 1. Participant must be at least 12 years of age. 2. Participant (or legal guardian) must understand and sign the protocol s willing to sign a consent form document. 3. Participant must have at least one definite pathogenic or likely pathogenic mutation in ABCA4 and a typical clinical presentation of Stargardt disease and phenotypic presentation of ABCA4 retinopathy in both eyes. 4. Participant must have at least two years of natural history data from at least four data points (a) The separation between any two consecutive data points must be at least six months (b) The most recent data point must be at least 4.5 months and no more than 16 months prior to the baseline visit (c) 1. Potential participants with three natural history data points may be enrolled to obtain their fourth natural history data point on protocol. 2. The separation between any two consecutive data points may fall short of 6 months by no more than 45 days; however, the total separation among the data points must allow for at least two years of natural history data. 3. Potential participants with four or more natural history data points completed off protocol, all of which having occurred more than 16 months prior to the baseline visit, may be enrolled to complete an additional natural history data point on protocol within the required timeframe from the baseline visit. 5. Participant must agree to adhere to Lifestyle Considerations throughout study duration. 6. Any female participant of childbearing potential must have a negative urine pregnancy test at screening and be willing to undergo urine pregnancy tests throughout the study. 7. Any female participant of childbearing potential must: - Have had a surgical sterilization OR - Completely abstain from intercourse OR ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

* INCLUSION CRITERIA: To be eligible, the following inclusion criteria must be met, where applicable. 1. Participant must be at least 12 years of age. 2. Participant (or legal guardian) must understand and sign the protocol s informed consent document. 3. Participant must have at least one definite pathogenic or likely pathogenic mutation in ABCA4 and a typical clinical presentation of Stargardt disease and phenotypic presentation of ABCA4 retinopathy in both eyes. 4. Participant must have at least two years of natural history data from at least four data points (a) The separation between any two consecutive data points must be at least six months (b) The most recent data point must be at least 4.5 months and no more than 16 months prior to the baseline visit (c) 1. Potential participants with three natural history data points may be enrolled to obtain their fourth natural history data point on protocol. 2. The separation between any two consecutive data points may fall short of 6 months by no more than 45 days; however, the total separation among the data points must allow for at least two years of natural history data. 3. Potential participants with four or more natural history data points completed off protocol, all of which having occurred more than 16 months prior to the baseline visit, may be enrolled to complete an additional natural history data point on protocol within the required timeframe from the baseline visit. 5. Participant must agree to adhere to Lifestyle Considerations throughout study duration. 6. Any female participant of childbearing potential must have a negative urine pregnancy test at screening and be willing to undergo urine pregnancy tests throughout the study. 7. Any female participant of childbearing potential must: * Have had a surgical sterilization OR * Completely abstain from intercourse OR * Practice at least one form of contraception while actively taking IP on the study and at least one week after IP discontinuation OR * Have a partner who had a surgical sterilization OR * Have a partner who practices one form of contraception while the female participant is actively taking IP and at least one week after the female participant discontinues IP. Any male participants must: * Have had a surgical sterilization OR * Completely abstain from intercourse OR * Practice at least one form of contraception while actively taking IP on the study and at least for 3 months after IP discontinuation OR * Have a partner who had a surgical sterilization OR * Have a partner who practices one form of contraception while the male participant actively takes IP and at least 3 months after the male participant discontinues IP. 1. Acceptable forms of surgical sterilization include: vasectomy, hysterectomy, or tubal ligation. 2. Acceptable methods of contraception include: hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring), intrauterine device, or barrier methods (diaphragm, condom) with spermicide. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: 1. Participant is actively receiving study IP in another investigational study. 2. Participant has a condition that would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control) by interfering with the participant s ability to engage in the required protocol evaluation and testing and/or comply with study visits. 3. Any female participant of childbearing potential that is pregnant or breast-feeding at the time of enrollment or planning to become pregnant during the study. 4. Participant has definitive pathogenic or likely pathogenic mutations in RDS/peripherin (PRPH2), PROM1, and/or ELOVL4. 5. Participant has a history of chronic renal impairment as measured in the acute care panel estimated glomerular filtration rate (eGFR)\<45 ml/min/1.73 m2) or severe hepatic, pulmonary, or cardiovascular disease (hypoxic state). 6. Participant is taking any medication that could adversely interact with metformin (e.g., cimetidine, furosemide, nifedipine) and cannot switch to an alternative medication. 7. Participant is currently taking metformin or participant has taken metformin during the period of natural history data collection that will be used for this study for a cumulative total of more than one month (\> 31 days). 8. Participant has a known hypersensitivity to metformin. 9. Participant has not stopped taking a glucagon-like peptide 1 (GLP-1) agonist at least two weeks prior to enrollment or is currently taking a GLP-1 agonist. 10. Participant has a history of chronic lactic acidosis, including diabetic ketoacidosis, with or without coma. 11. Participant has type 1 diabetes mellitus. 12. Scarring due to choroidal neovascularization (CNV) is present in either eye. QUALIFYING EYE ELIGIBILITY CRITERIA: In order to participate in the study, the participant must have at least one qualifying eye that meets all of the inclusion and none of the exclusion criteria listed below. Qualifying Eye Inclusion Criteria: 1\. A growth rate of square root AreaEZloss \> 0.025 mm/year based on calculation from natural history data. Qualifying Eye Exclusion Criteria: 1\. Retinal degeneration has advanced beyond a point where reliable measurement of the integrity of the IS-OS on OCT is possible.

Treatments Being Tested

DRUG

Metformin hydrochloride

Metformin is commercially produced in immediate and extended release. Participants will receive an immediate release formulation of metformin of 500mg daily at study entry. This dose will be titrated up weekly in 500mg increments to reach a goal of 2000mg daily maximum. Once participants \>=17 years of age reach 2000mg metformin immediate release they will switch to an extended-release formulation (1000mg twice a day by mouth). Participants \>= 17 years of age that cannot tolerate 2000mg will be permitted to reduce their daily dose to a minimum of 1000mg/day. Because metformin extended release is not FDA-approved for children under the age of 17, participants under 17 will remain on the immediate release formulation. For these participants who remain on standard formulation, the maximum tolerated dose between 1000mg and 2000mg/day will be given.

Locations (2)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

University of Michigan

Ann Arbor, Michigan, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT04545736), the sponsor (National Eye Institute (NEI)), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT04545736 clinical trial studying?

Who can participate in NCT04545736?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT04545736?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT04545736. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT04545736. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.