A Natural History of the Progression of Stargardt Disease: Retrospective and Prospective Studies

Completed

• Conditions: Stargardt Disease

• Registration Number: NCT01977846
• Lead Sponsor: Foundation Fighting Blindness

Brief Summary

Stargardt disease is currently an incurable and untreatable macular dystrophy that causes severe visual loss in children and young adults, thereby causing enormous morbidity with economic, psychological, emotional, and social implications. There are no FDA approved therapeutic treatments for this disease. Therefore, the objective of this study is to collect natural history data from a large population of children and adults in order to evaluate possible efficacy measures for planned clinical trials.

Participants will be recruited from each Investigator's own patient population as the study requires the availability of both multiyear retrospective data, as well as ongoing prospectively collected data. A concurrent ancillary study (SMART study) is also being conducted with a subset of the prospective study patients during their regular ProgSTAR study visits to expand the collection of retinal images to include microperimetry measurements gathered under scotopic (low light) conditions.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-08
• Study First Submitted: 2013-10-31
• Study First Submitted QC: 2013-10-31
• Study First Posted: 2013-11-07
• Primary Completion: 2017-02
• Study Completion: 2017-02
• Results First Submitted: 2018-05-30
• Status Verified: 2019-07
• Results First Submitted QC: 2019-10-30
• Last Update Submitted: 2019-10-30
• Results First Posted: 2019-11-01
• Last Update Posted: 2019-11-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 259

Inclusion Criteria

• Provide a signed informed consent form and authorization allowing the disclosure and use of protected health information.
• The designated primary study eye must have at least one well-demarcated area of atrophy as imaged by fundus autofluorescence with a minimum diameter of 300 microns and all lesions together must add to less than or equal to 12 mm2 (equivalent to no more than 5 disc areas in a least one eye) and a BCVA of 20 ETDRS letters (20/400 Snellen equivalent) or better.
• Two (2) pathogenic mutations confirmed present, in the ABCA4 gene. If only one ABCA4 allele contains a pathogenic mutation, the patient shall have a typical Stargardt phenotype, namely at least one eye must have flecks at the level of the retinal pigment epithelium typical for STGD.
• The primary study eye must have clear ocular media and adequate pupillary dilation to permit good quality fundus autofluorescence (FAF) and Spectral-Domain optical coherence tomography (sd-OCT) imaging in the opinion of the investigator.
• Be able to cooperate in performing the examinations.
• Be willing to undergo ocular examinations once every 6 months for up to 24 months.
• Be at least six years old.
• Both eyes can be included if inclusion criteria are fulfilled for both eyes.

Exclusion Criteria

• Ocular disease, such as choroidal neovascularization, glaucoma and diabetic retinopathy, in either eye that may confound assessment of the retina morphologically and functionally.
• Intraocular surgery in the primary study eye within 90 days prior to baseline visit.
• Current or previous participation in an interventional study to treat STGD such as gene therapy or stem cell therapy. Current participation in a drug trial or previous participation in a drug trial within six months before enrollment. The use of oral supplements of vitamins and minerals are permitted although the current use of Vitamin A supplementation shall be documented.
• The site Principal Investigator may declare any patient at their site ineligible to participate in the study for a sound medical reason prior to the patient's enrollment into the study.
• Any systemic disease with a limited survival prognosis (e.g. cancer, severe/unstable cardiovascular disease).
• Any condition that would interfere with the patient attending their regular follow-up visits every 6 months for up to 24 months, e.g. personality disorder, use of major tranquilizers such as Haldol or Phenothiazine, chronic alcoholism, Alzheimer's Disease or drug abuse.
• Evidence of significant uncontrolled concomitant diseases such as cardiovascular, neurological, pulmonary, renal, hepatic, endocrine or gastro-intestinal disorders.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Yearly Progression Rate of Atrophic Lesions Using Fundus Autofluorescence (FAF) Images	2-12 years	Yearly increase in area of decreased auto-fluorescence (DAF) which is defined as the sum of definite and questionable decreased auto-fluorescence

Secondary Outcome Measures

Name	Time	Method
Difference in the Rate of Retinal Sensitivity Change Per Year Between Photopic and Scotopic Micro-perimetry Testing	2 years	Difference in the yearly rate of change in retinal sensitivity under photopic and scotopic conditions. Sensitivity tested with a Nidek MP-1. Scotopic sensitivity was obtained using a 40 points test pattern, and photopic sensitivity was obtained using a 68 points test pattern in a subset of Prospective cohort patients
Yearly Rate of Loss of Retinal Sensitivity as Measured by Scotopic Microperimetry (MP)	2 years	The yearly rate of change in retinal sensitivity. Sensitivity tested with a Nidek MP-1 machine using a modified Humphrey 10-2 grid. The sensitivity was the average sensitivity from a 68-points test pattern (Prospective cohort only)
Yearly Rate of Loss of Overall Retinal Thickness	Participants followed at Baseline, 6 months, 12 months and 24 months	Yearly decrease of overall retinal thickness using spectral domain optical coherence tomography (SD-OCT) scans from a 20° x 20° scan area centered on the fovea. Data are only available for the Prospective cohort.
Yearly Rate of Loss of the Inner Ring Retinal Thickness	Participants followed at Baseline, 6 months, 12 months and 24 months	Yearly decrease of the inner ring retinal thickness using SD-OCT scans from a 20° x 20° scan area centered on the fovea. Inner ring defined as ETDRS fields 5-8. Data are only available for the Prospective cohort.
Yearly Rate of Loss of the Central Ring Retinal Thickness	Participants followed at Baseline, 6 months, 12 months and 24 months	Yearly decrease of the central ring retinal thickness using SD-OCT scans from a 20° x 20° scan area centered on the fovea. Central area defined as ETDRS fields 9. Data are only available for the Prospective cohort.
Yearly Rate of Visual Acuity Loss	2-12 years	Yearly change of visual acuity. Visual acuity measures of best-corrected or presenting VA extracted from medical record charts. Prospective cohort is best-corrected visual acuity using Early-Treatment Diabetic Retinopathy study methods
Yearly Rate of Loss of Outer Ring Retinal Thickness	Participants followed at Baseline, 6 months, 12 months and 24 months	Yearly decrease of outer ring retinal thickness using SD-OCT scans from a 20° x 20° scan area centered on the fovea. Outer ring defined as ETDRS fields 1-4.

Trial Locations

Locations (9)

Wilmer Eye Institute, Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Greater Baltimore Medical Center; 🇺🇸 Baltimore, Maryland, United States

Cole Eye Institute, Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Scheie Eye Institute, University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Retina Foundation of the Southwest; 🇺🇸 Dallas, Texas, United States

Moran Eye Center, University of Utah; 🇺🇸 Salt Lake City, Utah, United States

Moorfields Eye Hospital; 🇬🇧 London, United Kingdom

Institut de la Vision; 🇫🇷 Paris, France

Center for Ophthalmic Research, University of Teubingen; 🇩🇪 Tübingen, Germany