Oral Metformin for Stargardt Disease

Recruiting at 1 trial location

Overseen By Catherine Kangale Whitney, R.N.

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Eye Institute (NEI)

Must not be taking: Cimetidine, Furosemide, Nifedipine, GLP-1 agonists

Disqualifiers: Pregnancy, Chronic renal impairment, Type 1 diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 24 months

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether metformin, a common diabetes medication, can safely slow vision loss in people with ABCA4 retinopathy, a genetic eye disease. Researchers aim to determine if taking metformin orally for two years can help manage this condition. Individuals diagnosed with ABCA4 retinopathy and experiencing vision issues might be suitable for this study. Participants must be comfortable with regular eye exams and taking medication as part of the trial. As a Phase 1, Phase 2 trial, this research focuses on understanding how metformin works in people and measuring its effectiveness in managing vision loss, offering participants a chance to contribute to groundbreaking treatment development.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications that could interact negatively with metformin, such as cimetidine, furosemide, and nifedipine. Additionally, you must stop taking any glucagon-like peptide 1 (GLP-1) agonists at least two weeks before enrolling. If you are currently taking metformin, you cannot have taken it for more than one month during the natural history data collection period.

Is there any evidence suggesting that metformin is likely to be safe for humans?

A previous study linked metformin to a lower risk of developing dry age-related macular degeneration (AMD), another eye condition. This finding suggests that metformin might help protect the eyes. However, a main safety concern with metformin is a very rare but serious side effect called lactic acidosis, a build-up of lactic acid in the blood. Most people tolerate metformin well and do not experience this side effect.

This trial is in the early stages of testing for ABCA4 retinopathy. While some safety information is available, researchers are still gathering more data on its safety for this specific condition. The FDA has already approved metformin for other uses, such as managing diabetes, indicating a certain level of safety in humans. However, its safety for treating ABCA4 retinopathy specifically remains under study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Stargardt disease, which often focus on managing symptoms or slowing progression through vitamin supplementation and gene therapy, metformin offers a novel approach by potentially targeting the underlying mechanisms of the disease. Researchers are excited about metformin because it's traditionally used to treat diabetes and is now being explored for its ability to activate AMP-activated protein kinase (AMPK), which may protect retinal cells from degeneration. This new application of an established drug could offer a more direct method of preserving vision and slowing disease progression, providing hope for improved outcomes in Stargardt patients.

What evidence suggests that metformin might be an effective treatment for ABCA4 retinopathy?

Research has shown that metformin, which participants in this trial will receive, might help slow vision loss in people with Stargardt disease. Studies in mice lacking the ABCA4 protein indicate that metformin reduces harmful waste buildup in the eye and protects cells needed for vision. This suggests metformin could have a similar effect in humans by slowing the loss of these important cells. Additionally, some research suggests metformin might help with other eye conditions by lowering the risk of developing them. While clear evidence in humans for Stargardt disease is still developing, these findings are promising. ^{1 2 3 4 6}

Who Is on the Research Team?

Brian P Brooks, M.D.

Principal Investigator

National Eye Institute (NEI)

Are You a Good Fit for This Trial?

This trial is for people aged 12 and older with ABCA4 retinopathy, a genetic eye condition leading to vision loss. Participants must have documented changes in their condition over two years and agree to lifestyle guidelines and contraception if of childbearing potential.

Inclusion Criteria

Participant must agree to adhere to Lifestyle Considerations throughout study duration

Participant (or legal guardian) must understand and sign the protocol's informed consent document

Participant must have at least two years of natural history data from at least four data points with specific time intervals

Exclusion Criteria

Participant has a condition that would preclude participation in the study

I have scarring in my eye from abnormal blood vessel growth.

Participant is actively receiving study IP in another investigational study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Baseline assessments including medical history, eye exams, and various retinal tests

Baseline

1 visit (in-person)

Treatment

Participants take metformin by mouth for 24 months

24 months

Study visits every 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Metformin hydrochloride

Trial Overview The study tests whether metformin hydrochloride, an oral medication commonly used for diabetes, can slow down the progression of ABCA4 retinopathy when taken over a period of 24 months.

How Is the Trial Designed?

Group I: Metformin Experimental Treatment 1 Intervention

Oral administration of metformin

Who Is Running the Clinical Trial?

National Eye Institute (NEI)

Lead Sponsor

Trials

572

Recruited

1,320,000+

Published Research Related to This Trial

A study of eight patients with genetically-confirmed Stargardt disease (STGD1) revealed a retinal phenotype on SD-OCT that resembles hydroxychloroquine (HCQ) retinopathy, despite none of the patients having a history of HCQ use.

The findings suggest a phenotypic overlap between STGD1 and HCQ retinopathy, highlighting the importance of genetic screening to avoid misdiagnosis in patients presenting with similar retinal changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recessive Stargardt disease phenocopying hydroxychloroquine retinopathy. Nõupuu, K., Lee, W., Zernant, J., et al.[2019]

In a study of 234 patients with type 2 diabetes, those treated with metformin experienced significantly fewer ocular complications, such as glaucoma and diabetic retinopathy, compared to those using other oral antihyperglycemic agents.

After adjusting for various factors, metformin treatment was associated with a 86% reduction in the odds of developing glaucoma and a 67% reduction in the odds of diabetic retinopathy, suggesting a protective effect of metformin on eye health in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin use associated with protective effects for ocular complications in patients with type 2 diabetes - observational study. Maleškić, S., Kusturica, J., Gušić, E., et al.[2022]

In a study involving 34 eyes of patients with Stargardt Disease, 61.8% showed improvement in vision after treatment with autologous bone marrow-derived stem cells, with an average improvement of nearly 18%.

The treatment was safe, with no adverse events reported, and 94.1% of patients either improved or maintained their vision stability over a one-year follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem Cell Ophthalmology Treatment Study (SCOTS): Bone Marrow-Derived Stem Cells in the Treatment of Stargardt Disease. Weiss, JN., Levy, S.[2021]

There are currently eight ongoing clinical trials for Stargardt disease, focusing on various treatment strategies including gene therapy, neuroprotection, and stem cell therapy.

These trials aim to address the disease through different mechanisms, such as inhibiting toxic vitamin A dimers and restoring the function of the ABCA4 gene, which raises hope for effective treatments in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Tests Testing New Therapies for Stargardt Disease]. Kousal, B., Ďuďáková, Ľ., Hlavatá, L., et al.[2019]

Investigational therapies for Stargardt macular dystrophy (STGD1), including gene therapy and complement inhibitors, show promise in animal models but lack proven efficacy in human trials, highlighting the need for further research.

Visual cycle modulators (VCMs) like fenretinide and emixustat have not successfully improved vision in trials for age-related macular degeneration (AMD) and STGD1, indicating that while they are biologically plausible, their effectiveness remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stargardt macular dystrophy and evolving therapies. Hussain, RM., Ciulla, TA., Berrocal, AM., et al.[2019]

In a study involving healthy adults receiving intravenous infusions of 4-methylpyrazole (4-MP) or placebo, there were no significant differences in dark adaptation responses, indicating that 4-MP does not effectively inhibit the human visual cycle.

The results suggest that 4-MP is not a viable treatment option for Stargardt disease at this time, but further research in mouse models may still be valuable to explore its effects on lipofuscin production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of 4-methylpyrazole as a potential therapeutic dark adaptation inhibitor. Jurgensmeier, C., Bhosale, P., Bernstein, PS.[2018]

In a study of 217 patients with Stargardt disease, it was found that about 50% of eyes without definitely decreased autofluorescence (DDAF) at the first visit developed this lesion within 5 years, indicating that DDAF incidence could be a useful measure for evaluating treatment effectiveness.

The median time to develop DDAF lesions was 4.9 years, while for questionably decreased autofluorescence (QDAF) lesions it was 6.3 years, highlighting the progression of retinal damage in patients and the importance of monitoring these changes over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of Atrophic Lesions in Stargardt Disease in the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study: Report No. 5. Strauss, RW., Muñoz, B., Ho, A., et al.[2022]

In a study involving 23 subjects with Stargardt disease, emixustat demonstrated a dose-dependent effect on rod b-wave recovery rates, with the 10 mg dose showing near-complete suppression, indicating its potential efficacy in targeting RPE65.

The safety profile of emixustat was consistent with previous studies, primarily involving ocular adverse events, which suggests it may be a viable treatment option for Stargardt disease as it moves into a longer phase 3 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised study evaluating the pharmacodynamics of emixustat hydrochloride in subjects with macular atrophy secondary to Stargardt disease. Kubota, R., Birch, DG., Gregory, JK., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04545736

Oral Metformin for Treatment of ABCA4 Retinopathy The objective of this study is to investigate the safety and potential efficacy of oral metformin in slowing the rate of change in photoreceptor degeneration ...

2. nei.nih.gov nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/stargardt-disease/oral-metformin-treatment-abca4-retinopathy

Oral Metformin for Treatment of ABCA4 Retinopathy (Stargardt ... This is a safety and efficacy clinical trial that will investigate whether metformin can slow the progress of photoreceptor degeneration in ABCA4 retinopathy.

3. iovs.arvojournals.org iovs.arvojournals.org/article.aspx?articleid=2785783

Metformin Attenuates the Hallmarks of Stargardt Disease - IOVS Our findings imply that metformin may be an effective treatment for Stargardt disease. Furthermore, our study shows treatments targeting lipid handling defects ...

4. retinalphysician.com retinalphysician.com/issues/2025/october/novel-therapies-for-stargardt-disease/

Novel Therapies for Stargardt Disease Preclinical evidence in Abca4-/- mouse models demonstrated that metformin reduces lipofuscin buildup and photoreceptor loss, supporting its ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10440611/

Association of Metformin and Other Diabetes Medication Use ... Metformin use was associated with decreased odds of developing dry AMD. The protective effect was observed for cumulative 2-year doses below 601 g.

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/78/NCT02684578/Prot_SAP_000.pdf

METFORMIN CLINICAL TRIAL The greatest risk for patients taking metformin is the extremely rare but serious side- effect of lactic acidosis. Most reported cases of ...