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

Stargardt Disease Clinical Trial

— ProgSTAR  

Official title:

Natural History of Progression of Atrophy Secondary to Stargardt Disease: Retrospective, and Prospective Longitudinal Observational Study Incl. Ancillary SMART Study- Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01977846
• Other study ID #: FFBCRI-PROGSTAR-01/02
• Status: Completed
• Start date: August 2013
• Est. completion date: February 2017

Study information

• Verified date: July 2019
• Source: Foundation Fighting Blindness
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 259
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Macular Degeneration
• Stargardt Disease

Locations

Country	Name	City	State
France	Institut de la Vision	Paris
Germany	Center for Ophthalmic Research, University of Teubingen	Tübingen
United Kingdom	Moorfields Eye Hospital	London
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Wilmer Eye Institute, Johns Hopkins University	Baltimore	Maryland
United States	Cole Eye Institute, Cleveland Clinic	Cleveland	Ohio
United States	Retina Foundation of the Southwest	Dallas	Texas
United States	Scheie Eye Institute, University of Pennsylvania	Philadelphia	Pennsylvania
United States	Moran Eye Center, University of Utah	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Foundation Fighting Blindness	United States Department of Defense

Countries where clinical trial is conducted

United States,  France,  Germany,  United Kingdom, 

References & Publications (9)

Kong X, Fujinami K, Strauss RW, Munoz B, West SK, Cideciyan AV, Michaelides M, Ahmed M, Ervin AM, Schönbach E, Cheetham JK, Scholl HPN; ProgStar Study Group. Visual Acuity Change Over 24 Months and Its Association With Foveal Phenotype and Genotype in Ind — View Citation

Kong X, Strauss RW, Cideciyan AV, Michaelides M, Sahel JA, Munoz B, Ahmed M, Ervin AM, West SK, Cheetham JK, Scholl HPN; ProgStar Study Group. Visual Acuity Change over 12 Months in the Prospective Progression of Atrophy Secondary to Stargardt Disease (Pr — View Citation

Kong X, Strauss RW, Michaelides M, Cideciyan AV, Sahel JA, Muñoz B, West S, Scholl HP; ProgStar Study Group. Visual Acuity Loss and Associated Risk Factors in the Retrospective Progression of Stargardt Disease Study (ProgStar Report No. 2). Ophthalmology. — View Citation

Kong X, West SK, Strauss RW, Munoz B, Cideciyan AV, Michaelides M, Ho A, Ahmed M, Schönbach EM, Cheetham JK, Ervin AM, Scholl HPN; ProgStar study group. Progression of Visual Acuity and Fundus Autofluorescence in Recent-Onset Stargardt Disease: ProgStar Study Report #4. Ophthalmol Retina. 2017 Nov - Dec;1(6):514-523. doi: 10.1016/j.oret.2017.02.008. Epub 2017 Apr 28. — View Citation

Schönbach EM, Ibrahim MA, Strauss RW, Birch DG, Cideciyan AV, Hahn GA, Ho A, Kong X, Nasser F, Sunness JS, Zrenner E, Sadda SR, West SK, Scholl HPN; Progression of Stargardt Disease Study Group. Fixation Location and Stability Using the MP-1 Microperimeter in Stargardt Disease: ProgStar Report No. 3. Ophthalmol Retina. 2017 Jan - Feb;1(1):68-76. doi: 10.1016/j.oret.2016.08.009. Epub 2016 Oct 31. — View Citation

Schönbach EM, Wolfson Y, Strauss RW, Ibrahim MA, Kong X, Muñoz B, Birch DG, Cideciyan AV, Hahn GA, Nittala M, Sunness JS, Sadda SR, West SK, Scholl HPN; ProgStar Study Group. Macular Sensitivity Measured With Microperimetry in Stargardt Disease in the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study: Report No. 7. JAMA Ophthalmol. 2017 Jul 1;135(7):696-703. doi: 10.1001/jamaophthalmol.2017.1162. — View Citation

Strauss RW, Ho A, Muñoz B, Cideciyan AV, Sahel JA, Sunness JS, Birch DG, Bernstein PS, Michaelides M, Traboulsi EI, Zrenner E, Sadda S, Ervin AM, West S, Scholl HP; Progression of Stargardt Disease Study Group. The Natural History of the Progression of At — View Citation

Strauss RW, Muñoz B, Ho A, Jha A, Michaelides M, Cideciyan AV, Audo I, Birch DG, Hariri AH, Nittala MG, Sadda S, West S, Scholl HPN; ProgStar Study Group. Progression of Stargardt Disease as Determined by Fundus Autofluorescence in the Retrospective Progr — View Citation

Strauss RW, Muñoz B, Ho A, Jha A, Michaelides M, Mohand-Said S, Cideciyan AV, Birch D, Hariri AH, Nittala MG, Sadda S, Scholl HPN; ProgStar Study Group. Incidence of Atrophic Lesions in Stargardt Disease in the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study: Report No. 5. JAMA Ophthalmol. 2017 Jul 1;135(7):687-695. doi: 10.1001/jamaophthalmol.2017.1121. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Yearly Progression Rate of Atrophic Lesions Using Fundus Autofluorescence (FAF) Images	Yearly increase in area of decreased auto-fluorescence (DAF) which is defined as the sum of definite and questionable decreased auto-fluorescence	2-12 years
Secondary	Yearly Rate of Loss of Retinal Sensitivity as Measured by Scotopic Microperimetry (MP)	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)	2 years
Secondary	Yearly Rate of Visual Acuity Loss	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	2-12 years
Secondary	Difference in the Rate of Retinal Sensitivity Change Per Year Between Photopic and Scotopic Micro-perimetry Testing	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	2 years
Secondary	Yearly Rate of Loss of Overall Retinal Thickness	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.	Participants followed at Baseline, 6 months, 12 months and 24 months
Secondary	Yearly Rate of Loss of Outer Ring Retinal Thickness	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.	Participants followed at Baseline, 6 months, 12 months and 24 months
Secondary	Yearly Rate of Loss of the Inner Ring Retinal Thickness	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.	Participants followed at Baseline, 6 months, 12 months and 24 months
Secondary	Yearly Rate of Loss of the Central Ring Retinal Thickness	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.	Participants followed at Baseline, 6 months, 12 months and 24 months

External Links

•   Study Sponsor website
•   Study Website