Oral Metformin for Treatment of ABCA4 Retinopathy

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....

Conditions

• ABCA4 Retinopathy
• Stargardt Disease
• Retinal Dystrophy
• Retinal Degeneration

Interventions

DRUG

Metformin hydrochloride

Metformin is commercially produced in immediate and extended release. Participants will receive an immediate release formulation of metformin of 500mg daily at study entry. This dose will be titrated up weekly in 500mg increments to reach a goal of 2000mg daily maximum. Once participants \>=17 years of age reach 2000mg metformin immediate release they will switch to an extended-release formulation (1000mg twice a day by mouth). Participants \>= 17 years of age that cannot tolerate 2000mg will be permitted to reduce their daily dose to a minimum of 1000mg/day. Because metformin extended release is not FDA-approved for children under the age of 17, participants under 17 will remain on the immediate release formulation. For these participants who remain on standard formulation, the maximum tolerated dose between 1000mg and 2000mg/day will be given.

Sponsors & Collaborators

• National Eye Institute (NEI)

  lead NIH

Principal Investigators

• Brian P Brooks, M.D. · National Eye Institute (NEI)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

12 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-11-23

Primary Completion

2028-09-30

Completion

2028-09-30

FDA Drug

Yes

Countries

• United States

Study Locations