Ignite Creation Date:
2024-05-06 @ 3:11 PM
Last Modification Date:
2024-10-26 @ 1:44 PM
Study NCT ID:
NCT04545736
Status:
RECRUITING
Last Update Posted:
2024-06-14
First Post:
2020-09-10
Brief Title:
Oral Metformin for Treatment of ABCA4 Retinopathy
Sponsor:
National Eye Institute NEI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Oral Metformin for Treatment of ABCA4 Retinopathy
Status:
RECRUITING
Status Verified Date:
2024-10-22
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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
Detailed Description:
Study Description
ABCA4 retinopathy is an autosomal recessive progressive retinal dystrophy that leads to retinal pigment epithelium RPE and photoreceptor degeneration with consequent central visual loss A treatment that either reduces the rate of lipofuscin accumulation or improves the clearance of lipofuscin in the RPE could potentially slow the degeneration associated with this disease Metformin hydrochloride is a well-characterized commonly prescribed oral anti-diabetic medication that acts by suppressing liver gluconeogenesis and increasing peripheral insulin sensitivity
An additional effect of metformin is to increase macroautophagy via the Mammalian target of rapamycin complex 1 mTORC1AMP-activated Kinase AMPK pathway stimulation of this pathway would be predicted to enable the RPE to more efficiently handle lipofuscin This suggests an association between metformin use and slowing of retinal degeneration 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 in ABCA4 retinopathy
Objectives
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 in ABCA4 retinopathy
Endpoints
Primary Endpoint The difference in growth rate of square-root transformed area of EZ band loss square-root AreaEZloss from OCT between the pre-treatment phase and 24 month metformin treatment phase
Secondary Endpoints Proportion of participants with a 30 reduction in growth rate of square-root AreaEZloss during the treatment phase compared to the pre-treatment phase changes from baseline to Month 24 in Best-Corrected Visual Acuity BCVA total letters read perimetry and color fundus photography measurements and the change in rate of area of atrophy enlargement between the pre-treatment and 24-month metformin treatment phase
ABCA4 retinopathy is an autosomal recessive progressive retinal dystrophy that leads to retinal pigment epithelium RPE and photoreceptor degeneration with consequent central visual loss A treatment that either reduces the rate of lipofuscin accumulation or improves the clearance of lipofuscin in the RPE could potentially slow the degeneration associated with this disease Metformin hydrochloride is a well-characterized commonly prescribed oral anti-diabetic medication that acts by suppressing liver gluconeogenesis and increasing peripheral insulin sensitivity
An additional effect of metformin is to increase macroautophagy via the Mammalian target of rapamycin complex 1 mTORC1AMP-activated Kinase AMPK pathway stimulation of this pathway would be predicted to enable the RPE to more efficiently handle lipofuscin This suggests an association between metformin use and slowing of retinal degeneration 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 in ABCA4 retinopathy
Objectives
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 in ABCA4 retinopathy
Endpoints
Primary Endpoint The difference in growth rate of square-root transformed area of EZ band loss square-root AreaEZloss from OCT between the pre-treatment phase and 24 month metformin treatment phase
Secondary Endpoints Proportion of participants with a 30 reduction in growth rate of square-root AreaEZloss during the treatment phase compared to the pre-treatment phase changes from baseline to Month 24 in Best-Corrected Visual Acuity BCVA total letters read perimetry and color fundus photography measurements and the change in rate of area of atrophy enlargement between the pre-treatment and 24-month metformin treatment phase
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 20-EI-0163 | None | None | None |