Oral Metformin for Stargardt Disease

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Brian P Brooks, M.D.

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

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

Trial Summary

What is the purpose of 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....

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 metformin generally safe for humans?

Metformin, often used to treat type 2 diabetes, is generally considered safe for humans and has been associated with protective effects against eye complications in diabetic patients.

^{1 2 3 4 5}

How does the drug Metformin hydrochloride differ from other treatments for Stargardt Disease?

Metformin hydrochloride is unique for Stargardt Disease as it is an oral medication traditionally used to treat diabetes, whereas other potential treatments like gene therapy, stem cell therapy, and visual cycle modulators are more experimental and not yet approved. This approach is novel because it repurposes a well-known diabetes drug for a condition with no standard treatments.

^{2 3 6 7 8}

Eligibility Criteria

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

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

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

Exclusion Criteria

Participant has a condition that would preclude participation in the study

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

I have specific genetic mutations linked to my condition.

Trial Timeline

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

Participant Groups

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.

Group I: Metformin Experimental Treatment 1 Intervention

Oral administration of metformin

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center Bethesda, MD

University of Michigan Ann Arbor, MI

Who Is Running the Clinical Trial?

National Eye Institute (NEI) Lead Sponsor

References

1. Bosnia and Herzegovina pubmed.ncbi.nlm.nih.gov

Metformin use associated with protective effects for ocular complications in patients with type 2 diabetes - observational study. [2022] The aim was to study the association of the use of an oral antihyperglycemic agent metformin with the presence of ocular complications in patients with type 2 diabetes (T2D).

2. England pubmed.ncbi.nlm.nih.gov

Randomised study evaluating the pharmacodynamics of emixustat hydrochloride in subjects with macular atrophy secondary to Stargardt disease. [2022] Stargardt disease is a rare, inherited, degenerative disease of the retina that is the most common type of hereditary macular dystrophy. Currently, no approved treatments for the disease exist. The purpose of this study was to characterise the pharmacodynamics of emixustat, an orally available small molecule that targets the retinal pigment epithelium-specific 65 kDa protein (RPE65), in subjects with macular atrophy secondary to Stargardt disease.

3. England pubmed.ncbi.nlm.nih.gov

Stargardt macular dystrophy and evolving therapies. [2019] Stargardt macular dystrophy (STGD1) is a hereditary retinal degeneration that lacks effective treatment options. Gene therapy, stem cell therapy, and pharmacotherapy with visual cycle modulators (VCMs) and complement inhibitors are discussed as potential treatments.

4. Czech Republic pubmed.ncbi.nlm.nih.gov

[Clinical Tests Testing New Therapies for Stargardt Disease]. [2019] To provide information on currently ongoing clinical trials for Stargardt disease.

5. United States 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. [2022] Outcome measures that are sensitive to disease progression are needed as clinical end points for future treatment trials in Stargardt disease.

6. England pubmed.ncbi.nlm.nih.gov

Evaluation of 4-methylpyrazole as a potential therapeutic dark adaptation inhibitor. [2018] To investigate whether 4-methylpyrazole (4-MP; fomepizole; Antizol), an alcohol dehydrogenase inhibitor that delays dark adaptation in laboratory animals, is a possible pharmaceutical agent for the treatment of Stargardt disease.

7. Switzerland pubmed.ncbi.nlm.nih.gov

Stem Cell Ophthalmology Treatment Study (SCOTS): Bone Marrow-Derived Stem Cells in the Treatment of Stargardt Disease. [2021] Background: Stargardt Disease is the most common inherited macular degeneration, typically resulting in progressive central vision loss and legal blindness at an early age. We report regarding 34 eyes with Stargardt Disease treated in the Stem Cell Ophthalmology Treatment Study (SCOTS and SCOTS2). Methods: Autologous bone marrow was processed, separating the stem cell fraction which was provided Arms using retrobulbar, subtenons, intravitreal or subretinal and intravenous. The follow-up period was one year. Results: Of the 34 treated eyes, 21 (61.8%) improved, 8 (23.5%) remained stable, and 5 (14.7%) showed continued progression of their disease. Results were statistically significant with p = 0.0004. The average central vision improvement following treatment was 17.96% (95%CI, 16.39-19.53%) and ranged up to 80.5%. Of 17 patients treated, 13 (76.5%) showed visual acuity improvement in one or both eyes, 3 patients (17.6%) showed no net loss, and 1 worsened as a consequence of disease progression; 94.1% of patients had improved vision or remained stable. There were no adverse events. Conclusions: Patients with Stargardt Disease may potentially benefit from autologous bone marrow-derived stem cells (BMSC) as provided in SCOTS. Improvement or stabilization of vision was found to occur for the vast majority of reported patients and findings were highly statistically significant.

8. Germany pubmed.ncbi.nlm.nih.gov

Recessive Stargardt disease phenocopying hydroxychloroquine retinopathy. [2019] To describe a series of patients with Stargardt disease (STGD1) exhibiting a phenotype usually associated with hydroxychloroquine (HCQ) retinopathy on spectral domain-optical coherence tomography (SD-OCT).