Oral Metformin for Treatment of ABCA4 Retinopathy
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04545736|
Recruitment Status : Not yet recruiting
First Posted : September 11, 2020
Last Update Posted : November 25, 2020
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.
To see if metformin is safe and possibly helps to slow the rate of ABCA4 retinopathy.
People age 12 and older who have ABCA4 retinopathy and have problems with their vision.
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....
|Condition or disease||Intervention/treatment||Phase|
|ABCA4 Retinopathy Stargardt Disease Retinal Dystrophy Retinal Degeneration||Drug: Metformin hydrochloride||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||44 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Oral Metformin for Treatment of ABCA4 Retinopathy|
|Estimated Study Start Date :||November 30, 2020|
|Estimated Primary Completion Date :||August 31, 2026|
|Estimated Study Completion Date :||August 31, 2026|
Oral administration of metformin
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.
- The difference in growth rate of square-root transformed area of EZ band loss (square-root AreaEZloss) [ Time Frame: Pre-treatment, Baseline, Month 24 ]The difference in growth rate of square-root AreaEZloss, from OCT, between the pre-treatment phase and treatment phase.
- Proportion of participants with a 30% reduction in growth rate of square-root AreaEZloss [ Time Frame: Pre-treatment, Baseline, Month 24 ]Proportion of participants with 30% reduction in growth rate of square-root AreaEZloss, from OCT, during the treatment phase compared to the pre-treatment phase.
- Changes in best corrected visual acuity (BCVA) [ Time Frame: Baseline, Month 24 ]The change in BCVA total letters read from baseline to Month 24.
- Change in perimetry and color fundus photography measurements [ Time Frame: Baseline, Month 24 ]The change in perimetry and color fundus photography from baseline to Month 24.
- Change in rate of area of atrophy enlargement [ Time Frame: Pre-treatment, Baseline, Month 24 ]The difference in rate of region of atrophy measurements from FAF between the pre-treatment phase and treatment phase.
- Number and severity of adverse events [ Time Frame: ongoing throughout study ]The number and severity of systemic and ocular toxicities, adverse events and infections by severity, type and assessed relatedness to the IP throughout the study period.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04545736
|Contact: Allison T Bamji, R.N.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Brian P Brooks, M.D.||National Eye Institute (NEI)|