Stargardt-like Macular Dystrophy (STDG3) Secondary to Mutations in ELOVL4

An Observational Prospective Natural History Study of Stargardt-like Macular Dystrophy (STDG3) Secondary to Mutations in ELOVL4

Background:

STDG3 is an inherited eye disease. Currently there is no treatment for STDG3. Past studies of STDG3 have largely looked at members of large families at a single time point. Researchers want to learn more about the disease at an individual level.

Objective:

To understand the natural history of changes in the retina that occur in people with STDG3.

Eligibility:

People ages 10 and older with STDG3 due to a variant in the ELOVL4 gene.

Design:

Participants will have 6 visits. First they will have a screening visit, followed by a baseline visit. Then they will have a visit 6 months later. Then they will have a visit 1, 2, and 3 years after the first visit. Visits will last 4 to 8 hours.

Visits will include the following:

Medical history and physical exam.

Complete eye exam. Participants' eye pressure and ability to see letters on a vision chart will be tested. Their pupils will be dilated with eye drops. Pictures will be taken of the retina and the inside of the eye.

Questions about participants' family history, especially the presence of eye disease.

Visual field test. Participants will be seated in front of a large dome and asked to press a button when they see a light within the dome.

Electroretinogram. Participants will sit in the dark with their eyes patched for 30 minutes. Then they will wear special contact lenses and watch flashing lights.

Optical coherence tomography. Cross-sectional pictures will be taken of participants' retinas.

Fundus autofluorescence. Blue light will be shone into participants eyes to assess the health of the retina....

Study Overview

• Status: Recruiting
• Conditions: Stargardt-Like Macular Dystrophy

Detailed Description

Title: An Observational Prospective Natural History Study of Stargardt-like Macular Dystrophy (STDG3) Secondary to Mutations in ELOVL4

Study Description: Potential therapeutics for Stargardt-like macular dystrophy (STDG3) have been proposed. Cross-sectional studies of large families suggest progressive macular atrophy in STDG3 but there is a paucity of longitudinal data for these patients. The overall goal is to establish a natural history study of STDG3.

Objectives: The primary objective is to assess the longitudinal changes in retinal structure in STDG3 patients.

The secondary objective is to assess the longitudinal changes in retinal function in STDG3 patients.

An exploratory objective is to assess the longitudinal changes in functional vision and the participant s perceived effect on activities of daily living (e.g., mobility).

Endpoints: The primary endpoints are: A) the growth rate of the square root area of loss of the inner segment/outer segment band (EZband) obtained from spectral-domain optical coherence tomography (SD-OCT) and B) the rate of atrophy enlargement obtained from fundus autofluorescence

The secondary endpoints are: A) the change in BCVA total letters read from baseline to Year 3 and B) the rate of loss of retinal sensitivity measured with perimetry

Study Population: Up to 25 patients with Stargardt-like macular dystrophy 3 who are >= 10 years of age.

Description of Sites/Facilities Enrolling Participants: Patients will be seen in the Ophthalmic Genetics Clinic at the National Eye Institute within the NIH Clinical Center in Bethesda.

Study Duration: 84 months (7 years).

Participant Duration: 36 months (3 years).

• Study Type: Observational
• Enrollment (Estimated): 25

Contacts and Locations

• Study Contact: Name: Daniel W Claus, R.N.; Phone Number: (301) 451-1621; Email: daniel.claus@nih.gov
• Study Contact Backup: Name: Brett G Jeffrey, Ph.D.; Phone Number: (301) 402-2391; Email: jeffreybg@mail.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY8664111010 800-411-1222; Email: prpl@cc.nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

25 patients with Stargardt-like macular dystrophy 3 who are >= 10 years of age.

Description

• INCLUSION CRITERIA:

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

1. Stated willingness to comply with all study procedures and availability for the duration of the study.
2. Participant must be at least ten years of age.
3. Ability to perform required functional testing and ophthalmic imaging.
4. A mutation in ELOVL4 with a typical clinical presentation of Stargardt-like macular dystrophy.
5. Participant (or legal guardian) must understand and sign the protocol s informed consent document.

EXCLUSION CRITERIA:

A participant is not eligible if any of the following exclusion criteria are present.

1. Two or more definitive mutations in ABCA4 and/or one mutation in RDS/peripherin or PROM1.
2. Systemic medical contraindications that are rarely associated with ELOVL4 (e.g., Spinocerebellar Ataxia-34).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Affected; Patients with Stargardt-like macular dystrophy 3 who are >= 10 years of age.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Growth rate in square root area of loss of the inner segment/outer segment band (EZband)	The growth rate of the square root area of loss of the inner segment/outer segment band (EZband) obtained from SD-OCT.	Day 1, 182, 364, 728, 1,092
Growth rate of square root area of atrophy measured from short-wavelength autofluorescence	The rate of atrophy enlargement obtained from fundus autofluorescence.	Day 1, 182, 364, 728, 1,092

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in BCVA total letters read from baseline to Year 3	The change in BCVA total letters read from baseline to Year 3.	Day 1, 182, 364, 728, 1,092
The rate of loss of retinal sensitivity measured with perimetry	The rate of loss of retinal sensitivity measured with perimetry.	Day 1, 182, 364, 728, 1,092

Collaborators and Investigators

• Sponsor: National Eye Institute (NEI)
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Brett G Jeffrey, Ph.D., National Eye Institute (NEI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2022
• Primary Completion (Estimated): July 16, 2028
• Study Completion (Estimated): July 16, 2028

Study Registration Dates

• First Submitted: October 16, 2020
• First Submitted That Met QC Criteria: October 16, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): October 16, 2023
• Last Update Submitted That Met QC Criteria: October 13, 2023
• Last Verified: October 12, 2023

More Information

Terms related to this study

• Keywords: Natural History; ABCA4; Oral Metformin
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration
• Other Study ID Numbers: 10000108; 000108-EI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No