Oral Metformin for Treatment of ABCA4 Retinopathy
ABCA4 Retinopathy, Stargardt Disease, Retinal Dystrophy
About this trial
This is an interventional treatment trial for ABCA4 Retinopathy focused on measuring Stargardt Disease, Retinal Dystrophy, Retinal Degeneration
Eligibility Criteria
- INCLUSION CRITERIA:
To be eligible, the following inclusion criteria must be met, where applicable.
- Participant must be at least 12 years of age.
- Participant (or legal guardian) must understand and sign the protocol's informed consent document.
- Participant must have at least one definite mutation in ABCA4 and a typical clinical presentation of Stargardt disease.
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 4.5 months and no more than 16 months prior to the baseline visit.
- Participant must agree to adhere to Lifestyle Considerations throughout study duration.
- 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.
Female participant of childbearing potential and male participants or their partners 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 at least one acceptable method of contraception throughout the course of the study and for at least one week after IP discontinuation for female participants or for at least 3 months after IP discontinuation for male participants or their partnets. 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.
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
- Participant is actively receiving study IP in another investigational study.
- 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.
- Any female participant of childbearing potential that is pregnant, breast-feeding or planning to become pregnant during the study.
- Participant's retinal degeneration has advanced beyond a point where reliable measurement of the integrity of the IS-OS on OCT is not possible.
- Participant has definitive mutations in RDS/peripherin (PRPH2), PROM1, and/or ELOV4
- 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).
- Participant is taking any medication that could adversely interact with metformin (e.g., cimetidine, furosemide, nifedipine) and cannot switch to an alternative medication.
- Participant is currently taking metformin.
- Participant has a known hypersensitivity to metformin.
- Participant has a history of chronic lactic acidosis, including diabetic ketoacidosis, with or without coma.
- Participant has type 1 diabetes mellitus.
Sites / Locations
- National Institutes of Health Clinical CenterRecruiting
- University of MichiganRecruiting
Arms of the Study
Arm 1
Experimental
Metformin
Oral administration of metformin