Universal Rare Gene Study: A Registry and Natural History Study of Retinal Dystrophies Associated With Rare Disease-Causing Genetic Variants

NCT05589714 | Recruiting DMC

• 1 other identifier: Uni-Rare
• Study Type: observational
• Target: 1,500
• Locations: 14 countries
• Sites: 36

Brief Summary

This is an international, multicenter study with two components: Registry

• A standardized genetic screening and a prospective, standardized, cross-sectional clinical data collection
• Enrollment is open to all genes on the RD Rare Gene List Natural History Study
• A prospective, standardized, longitudinal Natural History Study
• Enrollment opens gene-by-gene, based on funding and within-gene Registry enrollment The study objectives are as follows. Registry Objectives
• Genotype Characterization
• Cross-Sectional Phenotype Characterization (within gene)
• Establish a Link to My Retina Tracker Registry (MRTR)
• Ancillary Exploratory Studies - Pooling of Genes
• Natural History (within gene)
• Structure-Function Relationship (within gene)
• Risk Factors for Progression (within gene)
• Ancillary Exploratory Studies - Pooling of Genes

Conditions

Retinitis Pigmentosa; Inherited Retinal Degeneration

Keywords

Inherited Retinal Degeneration

Outcome Measures

Primary Outcomes (11)

• Functional Outcome: Characterize change using Visual field sensitivity measured with quantitative topographic analysis (hill of vision [HOV])

  Measured by Static Perimetry (SP) using Octopus 900 Pro

  Baseline and every year until study completion (4 years)

• Functional Outcome: Characterize Change Using Early Treatment of Diabetic Retinopathy Study (ETDRS) / HOTV Best Corrected Visual Acuity (BCVA) letter score

  Measured by Electronic Visual Acuity (EVA) system or ETDRS/HOTV charts

  Baseline and every year until study completion (4 years)

• Functional Outcome: Characterize Change Using Low visual acuity test - for participants unable to see ETDRS letters

  Measured by Berkeley Rudimentary Vision Test (BRVT) for Low Visual Acuity

  Baseline and every year until study completion (4 years)

• Functional Outcome: Characterize Change Using ETDRS/HOTV best corrected low luminance visual acuity letter score

  Measured by Electronic Visual Acuity (EVA) system or ETDRS/HOTV charts

  Baseline and every year until study completion (4 years)

• Functional Outcome: Characterize Change in Mean retinal sensitivity

  Measured by Fundus guided Microperimetry (MP) using MAIA

  Baseline and every year until study completion (4 years)

• Functional Outcome: Characterize Change in Contrast sensitivity function

  Measured by Contrast sensitivity CSV-1000E chart

  Baseline and every year until study completion (4 years)

• Functional Outcome: Characterize Change in Retinal function using amplitudes and timing in response to rod- and cone-specific stimuli

  Measured by Full-field Electroretinogram (ffERG) Diagnosys Espion

  Baseline and at study completion (4 years)

• Functional Outcome: Characterize Change in Full-field retinal sensitivity

  Measured by Full-field stimulus threshold (FST) testing to blue, white, and red stimuli using Diagnosys Espion

  Baseline and every year until study completion (4 years)

• Functional Outcome: Characterize Change in Color vision function

  Measured by Color vision testing using Lanthony D15

  Baseline and every year until study completion (4 years)

• Structural Outcome: Characterize Change in Ellipsoid zone (EZ) area; outer nuclear layer and ganglion cell layer thicknesses

  Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) using Heidelberg Spectralis

  Baseline and every year until study completion (4 years)

• Structural Outcome: Characterize Change Using Qualitative and quantitative assessments of autofluorescence pattern

  Measured by Fundus Autofluorescence (FAF) using Optos

  Baseline and every year until study completion (4 years)

Study Arms (4)

Younger Age Cohort

Participants ages ≥ 4 years and \< 8 years old will be designated as the Younger Age Cohort. * Participants in this cohort will not be assigned a Vision Cohort. * Registry/Screening Visit and Natural History Study Visits will have an abbreviated testing schedule, detailed in the Schedule of Study Visits and Procedures table.

Vision Cohort 1

Participants who are aged ≥ 8 years old will be designated into a Vision Cohort based on data in the better eye, at the Registry/Screening Visit. Criteria that must be met in the better eye\* at the Registry/Screening Visit: visual acuity ETDRS letter score of 54 or more (approximate Snellen equivalent 20/80 or better) and visual field\*\* diameter 10 degrees or more in every meridian of the central field

Vision Cohort 2

Participants who are aged ≥ 8 years old will be designated into a Vision Cohort based on data in the better eye, at the Registry/Screening Visit. Criteria that must be met in the better eye\* at the Registry/Screening Visit: visual acuity ETDRS letter score of 19-53 (approximate Snellen equivalent 20/100 to 20/400) or visual acuity ETDRS letter score of 54 or more (approximate Snellen equivalent 20/80 or better) and visual field\*\* diameter less than 10 degrees in any meridian of the central field

Vision Cohort 3

Participants who are aged ≥ 8 years old will be designated into a Vision Cohort based on data in the better eye, at the Registry/Screening Visit. Criteria that must be met in the better eye\* at the Registry/Screening Visit: visual acuity ETDRS letter score of 18 or less (approximate Snellen equivalent 20/500 or worse)

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population includes patients with gene-related retinal degeneration. The universal registry is open to rare RD genes, to cross-sectionally characterize patients within rare RD genes (mild, moderate, and severe vision loss), so they are ready to be enrolled into a subsequent universal longitudinal natural history study as their gene is selected.

You may qualify if:

• Willing to participate in the study and able to communicate consent during the consent process
• Willing and able to complete all applicable Registry/Screening Visit assessments
• Age ≥ 4 years
• Must have a single gene on the RD Rare Gene List which meets one of the Genetic Screening Criteria below based on a genetic report\* from a clinically certified lab (or from a research lab which has been approved by the study Genetics Committee):
• Inheritance Pattern is Recessive and has at least 2 disease-causing variants which are homozygous or heterozygous in trans
• Inheritance Pattern is Recessive and has 2 disease-causing variants with unknown phase and meets all the following additional informatic criteria that is consistent with likely segregation in trans:
• Investigator confirms genotype and phenotype are consistent with autosomal recessive inheritance
• The 2 disease-causing variants have not been reported in cis in variant databases
• No additional potentially pathogenic variants were found on the gene (and the sequencing data for the gene were sufficiently robust to detect any additional potentially pathogenic variants)
• No potentially pathogenic variants were found in other common, likely candidate genes for the proposed condition
• Inheritance Pattern is Dominant, X-linked, or Mitochondrial and has at least 1 disease-causing variant
• Both eyes must meet the following criteria at the Registry/Screening Visit to enroll into the genetic screening phase:
• Both eyes must have a clinical diagnosis of retinal dystrophy
• Both eyes must permit good quality photographic imaging (e.g., but not limited to, clear ocular media, adequate pupil dilation, stable fixation)

You may not qualify if:

• \. History of more than 1 year of cumulative treatment, at any time, with an agent associated with pigmentary retinopathy including amiodarone, chloroquine, deferoxamine, hydroxychloroquine, pentosan polysulfate, tamoxifen, and deferoxamine Note: Since this is an observational study, pregnant women will not be specifically excluded from participation. However, minors that are pregnant shall be precluded from participation until they become the age of majority.
• Current vitreous hemorrhage
• Current complications of pathological myopia (for example, but not limited to, myopic maculopathy including atrophy, scar, choroidal neovascularization, schisis) that could inhibit ability to obtain good quality photographic imaging
• History of intraocular surgery (for example, but not limited to, cataract surgery, vitrectomy, penetrating keratoplasty, or LASIK) within 3 months of Registry/Screening Visit
• Current or any history of confirmed diagnosis of glaucoma (for example, but not limited to, glaucomatous VF changes or nerve changes, or history of glaucoma filtering surgery)
• Current or any history of retinal vascular occlusion or proliferative diabetic retinopathy
• History or current evidence of ocular disease that, in the opinion of the Investigator, may confound assessment of visual function (for example, but not limited to, tractional or rhegmatogenous retinal detachment, any vitreoretinal surgery, retinal vascular occlusion, proliferative diabetic retinopathy)
• The following medications and treatments are prohibited as they can affect progression of retinitis pigmentosa (RP). The participant must not have received the following treatments:
• Any use of ocular stem cell or gene therapy Any treatment with ocriplasmin Treatment with Ozurdex (dexamethasone), Iluvien, or Yutiq (fluocinolone acetonide) intravitreal implant
• The following medications and treatments are excluded within the specified timeframe:
• Treatment with an ophthalmic oligonucleotide within the last 9 months (last treatment date is less than 9 months prior to Registry/Screening Visit date)
• Treatment with any other product within five times the expected half-life of the product (time from last treatment date to Registry/Screening Visit date is at least 5 times the half-life of the given product)

Sponsors & Collaborators

• Jaeb Center for Health Research: lead
• Foundation Fighting Blindness: collaborator

Study Sites (36)

University of Arkansas, Jones Eye Institute

Little Rock, Arkansas, 72205, United States

RECRUITING

USC Roski Eye Institute

Los Angeles, California, 90033, United States

NOT YET RECRUITING

University of California San Francisco

San Francisco, California, 94158, United States

RECRUITING

University of Florida Health Jacksonville

Jacksonville, Florida, 32209, United States

RECRUITING

University of Miami, Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

RECRUITING

Emory University, Emory Eye Center

Atlanta, Georgia, 30322, United States

RECRUITING

Johns Hopkins University, Wilmer Eye Institute

Baltimore, Maryland, 21236, United States

RECRUITING

Harvard Univ., Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

RECRUITING

University of Michigan, Kellogg Eye Center

Ann Arbor, Michigan, 48105, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Duke University, Duke Eye Center

Durham, North Carolina, 27705, United States

RECRUITING

Oregon Health & Science Univ., Casey Eye Institute

Portland, Oregon, 97239, United States

RECRUITING

University of Pennsylvania, Scheie Eye Institute

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

UPMC Eye Center

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

RECRUITING

Baylor College of Medicine, Alkek Eye Center

Houston, Texas, 77030, United States

RECRUITING

University of Utah, John Moran Eye Center

Salt Lake City, Utah, 84132, United States

RECRUITING

University of Wisconsin Madison

Madison, Wisconsin, 53711, United States

RECRUITING

Medical College of Wisconsin Eye Institute

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Centre for Eye Research Australia

East Melbourne, Victoria, Australia

RECRUITING

Ghent University

Ghent, Belgium

NOT YET RECRUITING

INRET Clínica e Centro de Pesquisa

Belo Horizonte, Minas Gerais, 30150-270, Brazil

RECRUITING

Instituto de Genética Ocular

São Paulo, São Paulo Province, Brazil

RECRUITING

University of Alberta and Alberta Health Services

Edmonton, Alberta, Canada

RECRUITING

University of Toronto, Hospital for Sick Children

Toronto, Ontario, M5G 2L3, Canada

RECRUITING

University Health Network

Toronto, M5T 2S8, Canada

RECRUITING

Helsinki University Hospital

Helsinki, 00100, Finland

RECRUITING

CHNO des Quinze-Vingts

Paris, 75012, France

RECRUITING

Hadassah-Hebrew University Medical Center

Jerusalem, 9112001, Israel

RECRUITING

Vista Vision Eye Clinic

Brescia, 25123, Italy

RECRUITING

Retina and Genomics Institute

Yucatán, Merida, Mexico

RECRUITING

Radboud University Medical Center

Nijmegen, 6525 GA, Netherlands

RECRUITING

Oslo University Hospital

Oslo, Norway

NOT YET RECRUITING

University Hospital Basel

Basel, Canton of Basel-City, Switzerland

RECRUITING

University Hospital Jules-Gonin

Lausanne, 1004, Switzerland

RECRUITING

Moorfields Eye Hospital

London, EC1V 2PD, United Kingdom

RECRUITING

Related Links

• Foundation Fighting Blindness Public Website
• Uni-Rare Rare Gene List

MeSH Terms

Conditions

Retinitis Pigmentosa

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• José-Alain Sahel, MD

  Director, UPMC Eye Center University of Pittsburgh School of Medicine

  STUDY CHAIR

Central Study Contacts

Coordinating Center

CONTACT

813-975-8690; ffb@jaeb.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2022
• First Posted: October 21, 2022
• Study Start: May 11, 2023
• Primary Completion (Estimated): December 15, 2029
• Study Completion (Estimated): December 15, 2030
• Last Updated: April 14, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: After manuscript is published
• Access Criteria: Users accessing data must enter an email address

Locations

IT (1); NL (1); NO (1); FR (1); BR (2); CH (2); IL (1); GB (1); FI (1); US (19); BE (1); ME (1); CA (3); AU (1)