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

• ClinicalTrials.gov Identifier: NCT04591483
• Recruitment Status: Recruiting
• First Posted: October 19, 2020
• Last Update Posted: January 22, 2021
• Sponsor: National Eye Institute (NEI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )

Tracking Information

• First Submitted Date: October 16, 2020
• First Posted Date: October 19, 2020
• Last Update Posted Date: January 22, 2021
• Estimated Study Start Date: January 27, 2021
• Estimated Primary Completion Date: July 16, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 16, 2020)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 16, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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 5 visits. First they will have a screening 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....

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
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: 25 patients with Stargardt-like macular dystrophy 3 who are >= 10 years of age.
• Condition: Stargardt-Like Macular Dystrophy
• Intervention: Not Provided

Study Groups/Cohorts

Affected

Patients with Stargardt-like macular dystrophy3 who are >= 10 years of age.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 16, 2020): 25
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 16, 2025
• Estimated Primary Completion Date: July 16, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

• 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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 10 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Brett G Jeffrey, Ph.D.; (301) 402-2391; jeffreybg@mail.nih.gov

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04591483
• Other Study ID Numbers: 10000108; 000108-EI
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
• Study Sponsor: National Eye Institute (NEI)
• Collaborators: Not Provided

Investigators

• Principal Investigator: Brett G Jeffrey, Ph.D.; National Eye Institute (NEI)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: October 13, 2020