Oral Metformin for Treatment of ABCA4 Retinopathy

• Status: Recruiting
• Trial end date: 2026-08-31
• Target enrollment: 0
• Participant gender: All

Summary

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....

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Eye Institute (NEI)
• Treatments: Metformin

Criteria

• 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 mutation in ABCA4 and a typical clinical presentation of Stargardt disease.

4. Participant must have at least two years of natural history data with a rate of growth of square-root(Area(EZloss)) > 0.025 mm/year based on calculation from at least four data points.*

The four data points must be at least six months apart and the most recent data point must be at least six months and no more than 16 months prior to 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 (or have a partner who has) had a surgical sterilization (vasectomy, hysterectomy, or tubal ligation), be completely abstinent from intercourse or must agree to practice two acceptable methods of contraception throughout the course of the study and for at least one week after IP discontinuation. Acceptable methods of contraception include:

• hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring),

• intrauterine device,

• barrier methods (diaphragm, condom) with spermicide.

Metformin, like insulin, is considered a class B drug by the FDA (animal reproductive studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women) and is frequently prescribed for gestational diabetes. One meta-analysis showed outcomes with metformin were slightly superior to insulin. Nonetheless, out of an abundance of caution, we will ask female, but not male, participants in this trial to use these forms of contraception.

*This will most likely be obtained through the existing NEI protocol 12-EI-0203, but participants outside this study will be considered if they meet the requisite criteria.

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, breast-feeding or planning to become pregnant during the study.

4. Participant's retinal degeneration has advanced beyond a point where reliable measurement of the integrity of the IS-OS on OCT is not possible.

5. Participant has definitive mutations in RDS/peripherin (PRPH2), PROM1, and/or ELOV4

6. Participant has a history of chronic renal impairment as measured in the acute care panel (estimated glomerular filtration rate (eGFR)<45ml/min/1.73m^2) or severe hepatic, pulmonary, or cardiovascular disease (hypoxic state).

7. Participant is taking any medication that could adversely interact with metformin (e.g., cimetidine, furosemide, nifedipine) and cannot switch to an alternative medication.

8. Participant is currently taking metformin.

9. Participant has a known hypersensitivity to metformin.

10. Participant has a history of chronic lactic acidosis, including diabetic ketoacidosis, with or without coma.

11. Participant has type 1 diabetes mellitus.