RECRUITING

Oral Metformin for Treatment of ABCA4 Retinopathy

Conditions

ABCA4 Retinopathy Stargardt Disease Retinal Dystrophy Retinal Degeneration

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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....

Official Title

Oral Metformin for Treatment of ABCA4 Retinopathy

Quick Facts

Study Start:2020-11-23

Study Completion:2027-08-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04545736

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years to 100 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Participant must be at least 12 years of age. 2. Participant (or legal guardian) must understand and sign the protocol's informed consent document. 3. Participant must have at least one definite pathogenic or likely pathogenic mutation in ABCA4 and a typical clinical presentation of Stargardt disease and phenotypic presentation of ABCA4 retinopathy in both eyes. 4. Participant must have at least two years of natural history data from at least four data points (a). The separation between any two consecutive data points must be at least six months (b). The most recent data point must be at least 4.5 months and no more than 16 months prior to the baseline visit (c). 1. Potential participants with three natural history data points may be enrolled to obtain their fourth natural history data point on protocol. 2. The separation between any two consecutive data points may fall short of 6 months by no more than 45 days; however, the total separation among the data points must allow for at least two years of natural history data. 3. Potential participants with four or more natural history data points completed off protocol, all of which having occurred more than 16 months prior to the baseline visit, may be enrolled to complete an additional natural history data point on protocol within the required timeframe from the baseline visit. 5. Participant must agree to adhere to Lifestyle Considerations throughout study duration. 6. 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. 7. Any female participant of childbearing potential must: * Have had a surgical sterilizationa OR * Completely abstain from intercourse OR * Practice at least one form of contraceptionb during the study and at least one week after IP discontinuation OR * Have a partner who had a surgical sterilization OR * Have a partner who practices one form of contraception for the duration of the study and at least one week after the female participant discontinues IP. * Have had a surgical sterilization (a) OR * Completely abstain from intercourse OR * Practice at least one form of contraception (b) throughout the study and at least for 3 months after IP discontinuation OR * Have a partner who had a surgical sterilization OR * Have a partner who practices one form of contraception for the duration of the study and at least 3 months after the male participant discontinues IP. 1. Acceptable forms of surgical sterilization include: vasectomy, hysterectomy, or tubal ligation. 2. Acceptable methods of contraception include: hormonal contraception (i.e., birth control pills, injected hormones, dermal	1. Participant is actively receiving study IP in another investigational study. 2. Participant has a condition that would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control) by interfering with the participant's ability to engage in the required protocol evaluation and testing and/or comply with study visits. 3. Any female participant of childbearing potential that is pregnant, breast-feeding or planning to become pregnant during the study. 4. Participant has definitive pathogenic or likely pathogenic mutations in RDS/peripherin (PRPH2), PROM1, and/or ELOVL4. 5. Participant has a history of chronic renal impairment as measured in the acute care panel estimated glomerular filtration rate (eGFR\<45 ml/min/1.73 m2) or severe hepatic, pulmonary, or cardiovascular disease (hypoxic state). 6. Participant is taking any medication that could adversely interact with metformin (e.g., cimetidine, furosemide, nifedipine) and cannot switch to an alternative medication. 7. Participant is currently taking metformin or participant has taken metformin during the period of natural history data collection that will be used for this study for a cumulative total of more than one month (\> 31 days). 8. Participant has a known hypersensitivity to metformin. 9. Participant has a history of chronic lactic acidosis, including diabetic ketoacidosis, with or without coma. 10. Participant has type 1 diabetes mellitus. 11. Scarring due to choroidal neovascularization (CNV) is present in either eye.

Inclusion Criteria

Exclusion Criteria

1. Participant must be at least 12 years of age.
2. Participant (or legal guardian) must understand and sign the protocol's informed consent document.
3. Participant must have at least one definite pathogenic or likely pathogenic mutation in ABCA4 and a typical clinical presentation of Stargardt disease and phenotypic presentation of ABCA4 retinopathy in both eyes.
4. Participant must have at least two years of natural history data from at least four data points (a). The separation between any two consecutive data points must be at least six months (b). The most recent data point must be at least 4.5 months and no more than 16 months prior to the baseline visit (c).
1. Potential participants with three natural history data points may be enrolled to obtain their fourth natural history data point on protocol.
2. The separation between any two consecutive data points may fall short of 6 months by no more than 45 days; however, the total separation among the data points must allow for at least two years of natural history data.
3. Potential participants with four or more natural history data points completed off protocol, all of which having occurred more than 16 months prior to the baseline visit, may be enrolled to complete an additional natural history data point on protocol within the required timeframe from the baseline visit.
5. Participant must agree to adhere to Lifestyle Considerations throughout study duration.
6. 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.
7. Any female participant of childbearing potential must:
* Have had a surgical sterilizationa OR
* Completely abstain from intercourse OR
* Practice at least one form of contraceptionb during the study and at least one week after IP discontinuation OR
* Have a partner who had a surgical sterilization OR
* Have a partner who practices one form of contraception for the duration of the study and at least one week after the female participant discontinues IP.
* Have had a surgical sterilization (a) OR
* Completely abstain from intercourse OR
* Practice at least one form of contraception (b) throughout the study and at least for 3 months after IP discontinuation OR
* Have a partner who had a surgical sterilization OR
* Have a partner who practices one form of contraception for the duration of the study and at least 3 months after the male participant discontinues IP.
1. Acceptable forms of surgical sterilization include: vasectomy, hysterectomy, or tubal ligation.
2. Acceptable methods of contraception include: hormonal contraception (i.e., birth control pills, injected hormones, dermal

1. Participant is actively receiving study IP in another investigational study.
2. Participant has a condition that would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control) by interfering with the participant's ability to engage in the required protocol evaluation and testing and/or comply with study visits.
3. Any female participant of childbearing potential that is pregnant, breast-feeding or planning to become pregnant during the study.
4. Participant has definitive pathogenic or likely pathogenic mutations in RDS/peripherin (PRPH2), PROM1, and/or ELOVL4.
5. Participant has a history of chronic renal impairment as measured in the acute care panel estimated glomerular filtration rate (eGFR\<45 ml/min/1.73 m2) or severe hepatic, pulmonary, or cardiovascular disease (hypoxic state).
6. Participant is taking any medication that could adversely interact with metformin (e.g., cimetidine, furosemide, nifedipine) and cannot switch to an alternative medication.
7. Participant is currently taking metformin or participant has taken metformin during the period of natural history data collection that will be used for this study for a cumulative total of more than one month (\> 31 days).
8. Participant has a known hypersensitivity to metformin.
9. Participant has a history of chronic lactic acidosis, including diabetic ketoacidosis, with or without coma.
10. Participant has type 1 diabetes mellitus.
11. Scarring due to choroidal neovascularization (CNV) is present in either eye.

Contacts and Locations

Study Contact

Cathy Kangale-Whitney, R.N.

CONTACT

(301) 402-4174

cathy.kangale-whitney@nih.gov

Brian P Brooks, M.D.

CONTACT

(301) 496-3577

brooksb@mail.nih.gov

Principal Investigator

Brian P Brooks, M.D.

PRINCIPAL_INVESTIGATOR

National Eye Institute (NEI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

University of Michigan

Ann Arbor, Michigan, 48109-0624

United States

Collaborators and Investigators

Sponsor: National Eye Institute (NEI)

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

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-11-23

Study Completion Date2027-08-31

Study Record Updates

Study Start Date2020-11-23

Study Completion Date2027-08-31

Terms related to this study

Keywords Provided by Researchers

Stargardt Disease
Retinal Dystrophy
Retinal Degeneration

Additional Relevant MeSH Terms

ABCA4 Retinopathy
Stargardt Disease
Retinal Dystrophy
Retinal Degeneration