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Trial record 30 of 36 for:    stargardt

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
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )

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....


Condition or disease Intervention/treatment Phase
ABCA4 Retinopathy Stargardt Disease Retinal Dystrophy Retinal Degeneration Drug: Metformin hydrochloride Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
Experimental: Metformin
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. Changes in best corrected visual acuity (BCVA) [ Time Frame: Baseline, Month 24 ]
    The change in BCVA total letters read from baseline to Month 24.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

To be eligible, the following inclusion criteria must be met, where applicable.

  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 mutation in ABCA4 and a typical clinical presentation of Stargardt disease.
  4. Participant must have at least two years of natural history data with a rate of growth of square-root(Area(EZloss)) > 0.025 mm/year based on calculation from at least four data points.*

    The four data points must be at least six months apart and the most recent data point must be at least six months and no more than 16 months prior to 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 (or have a partner who has) had a surgical sterilization (vasectomy, hysterectomy, or tubal ligation), be completely abstinent from intercourse or must agree to practice two acceptable methods of contraception throughout the course of the study and for at least one week after IP discontinuation. Acceptable methods of contraception include:

    • hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring),
    • intrauterine device,
    • barrier methods (diaphragm, condom) with spermicide.

Metformin, like insulin, is considered a class B drug by the FDA (animal reproductive studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women) and is frequently prescribed for gestational diabetes. One meta-analysis showed outcomes with metformin were slightly superior to insulin. Nonetheless, out of an abundance of caution, we will ask female, but not male, participants in this trial to use these forms of contraception.

*This will most likely be obtained through the existing NEI protocol 12-EI-0203, but participants outside this study will be considered if they meet the requisite criteria.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

  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's retinal degeneration has advanced beyond a point where reliable measurement of the integrity of the inner and outer segment junction (IS-OS) on OCT is not possible.
  5. Participant has definitive mutations in RDS/peripherin, PROM1, and/or ELOV4
  6. Participant has a history of chronic renal impairment as measured in the acute care panel (estimated glomerular filtration rate (eGFR)<45ml/min/1.73m^2) or severe hepatic, pulmonary, or cardiovascular disease (hypoxic state).
  7. Participant is taking any medication that could adversely interact with metformin (e.g., cimetidine, furosemide, nifedipine) and cannot switch to an alternative medication.
  8. Participant is currently taking metformin.
  9. Participant has a known hypersensitivity to metformin.
  10. Participant has a history of chronic lactic acidosis, including diabetic ketoacidosis, with or without coma.
  11. Participant has type 1 diabetes mellitus.

Information from the National Library of Medicine

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


Contacts
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Contact: Allison T Bamji, R.N. (301) 451-3437 bamjia@nei.nih.gov

Locations
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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    prpl@cc.nih.gov   
Sponsors and Collaborators
National Eye Institute (NEI)
Investigators
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Principal Investigator: Brian P Brooks, M.D. National Eye Institute (NEI)
Additional Information:
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Responsible Party: National Eye Institute (NEI)
ClinicalTrials.gov Identifier: NCT04545736    
Other Study ID Numbers: 200163
20-EI-0163
First Posted: September 11, 2020    Key Record Dates
Last Update Posted: November 25, 2020
Last Verified: September 9, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) ):
Stargardt Disease
Retinal Dystrophy
Retinal Degeneration
Additional relevant MeSH terms:
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Retinal Diseases
Retinal Degeneration
Retinal Dystrophies
Eye Diseases
Eye Diseases, Hereditary
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs