NCT04545736

Oral Metformin for Treatment of ABCA4 Retinopathy

Recruiting now Phase 1, PHASE2 Last updated 27 October 2025

What this trial tests

Phase 1, PHASE2 trial testing Metformin hydrochloride in ABCA4 Retinopathy in 56 participants. Currently enrolling.

Timeline

23 November 2020

Primary endpoint
30 September 2028

30 September 2028

Quick facts

Lead sponsor	National Eye Institute (NEI)
Phase	Phase 1, PHASE2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	56
Start date	23 November 2020
Primary completion	30 September 2028
Estimated completion	30 September 2028
Sites	2 locations across United States

Drugs / interventions tested

• Metformin hydrochloride — full drug profile →

Conditions studied

• ABCA4 Retinopathy — all drugs for ABCA4 Retinopathy →
• Stargardt Disease — all drugs for Stargardt Disease →
• Retinal Dystrophy — all drugs for Retinal Dystrophy →
• Retinal Degeneration — all drugs for Retinal Degeneration →

Sponsor

National Eye Institute (NEI)

Who can join

Adults 12 to 100, any sex, with ABCA4 Retinopathy or Stargardt Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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....

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Stargardt macular dystrophy and therapeutic approaches.
   Fujinami K, Waheed N, Laich Y, Yang P, et al · · 2024 · cited 20× · PMID 37940365 · DOI 10.1136/bjo-2022-323071
2. Emerging Therapeutic Approaches and Genetic Insights in Stargardt Disease: A Comprehensive Review.
   Ghenciu LA, Hațegan OA, Stoicescu ER, Iacob R, et al · · 2024 · cited 19× · PMID 39201545 · DOI 10.3390/ijms25168859
3. Photoreceptor degeneration in ABCA4-associated retinopathy and its genetic correlates.
   Pfau M, Cukras CA, Huryn LA, Zein WM, et al · · 2022 · cited 19× · PMID 35076026 · DOI 10.1172/jci.insight.155373
4. Association of Metformin and Other Diabetes Medication Use and the Development of New-Onset Dry Age-Related Macular Degeneration: A Case-Control Study.
   Kaufmann GT, Hyman MJ, Gonnah R, Hariprasad S, et al · · 2023 · cited 10× · PMID 37589984 · DOI 10.1167/iovs.64.11.22
5. Effects of medications on hypoxia-inducible factor in the retina: A review.
   Kim AH, Kolesnikova M, Ngo WK, Tsang SH. · · 2023 · cited 10× · PMID 36594241 · DOI 10.1111/ceo.14161
6. The ABCs of Stargardt disease: the latest advances in precision medicine.
   Zaydon YA, Tsang SH. · · 2024 · cited 9× · PMID 39060921 · DOI 10.1186/s13578-024-01272-y
7. Updates on Emerging Interventions for Autosomal Recessive <i>ABCA4</i>-Associated Stargardt Disease.
   Wang L, Shah SM, Mangwani-Mordani S, Gregori NZ. · · 2023 · cited 8× · PMID 37834872 · DOI 10.3390/jcm12196229
8. Stargardt disease-associated in-frame ABCA4 exon 17 skipping results in significant ABCA4 function.
   Kaltak M, Blanco-Garavito R, Molday LL, Dhaenens CM, et al · · 2023 · cited 8× · PMID 37587475 · DOI 10.1186/s12967-023-04406-x