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

NCT ID: NCT05589714

Last Updated: 2026-02-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

1500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-05-11

Study Completion Date

2030-12-15

Brief Summary

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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

1. Genotype Characterization
2. Cross-Sectional Phenotype Characterization (within gene)
3. Establish a Link to My Retina Tracker Registry (MRTR)
4. Ancillary Exploratory Studies - Pooling of Genes

Natural History Study Objectives

1. Natural History (within gene)
2. Structure-Function Relationship (within gene)
3. Risk Factors for Progression (within gene)
4. Ancillary Exploratory Studies - Pooling of Genes

Detailed Description

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This study includes multiple phases.

1. Screening Phase

The patient's current genetic report will be reviewed. Genetic testing will not be performed in this study. A prior conclusive genetic test will be assessed for screening analysis. Having at least one gene on the RD Rare Gene List meets one of the eligible Genetic Screening Criteria and other eligibility criteria can be evaluated based on medical history.
2. Genetic Screening Phase:

Genetic reports for participants enrolled into the genetic screening phase will be uploaded to study website for review and confirmation by Central Genetics Auditor (CGA) as meeting Genetic Screening Criteria.Participants confirmed as meeting those criteria will be considered enrolled into the Registry.
3. Registry Phase:

The flow of participants who are enrolled into the Registry depends on whether their causal gene is designated as a Natural History Study (NHS) Target Gene. If they are not Designated as NHS Target Gene, they will receive annual phone calls up to 48 months from the Registry/Screening visit or until the gene is designated as NHS Target Gene. If they are Designated as NHS Target Gene participants will be considered pending enrollment into the NHS.

The Registry will establish genetically and clinically well-characterized cohorts of patients across hundreds of genetic variants associated with retinal dystrophy (RD). Characterization of these patients will accelerate eligibility screening for the Natural History Study, provide cross-sectional data on phenotype-genotype associations, and contribute to our knowledge of pathogenicity of these rare disease-causing variants.
4. Natural History Study (NHS) Phase

Participants pending enrollment will return to the clinic for the NHS Enrollment/Baseline Visit and return to the clinic for follow-up visits.

The Natural History Study will accelerate the identification and development of sensitive, reliable outcome measures for clinical trials, which will facilitate development of treatments for retinal dystrophies due to disease-causing genetic variants. The expected impact of the Natural History Study is as follows:

1. Describe the natural history of retinal degeneration in patients with rare disease-causing genetic variants
2. Identify sensitive structural and functional outcome
3. Identify well-defined subpopulations for future clinical trials of investigative treatments for rare inherited retinal degeneration

Conditions

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Inherited Retinal Degeneration Retinitis Pigmentosa

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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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.

No interventions assigned to this group

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

No interventions assigned to this group

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

No interventions assigned to this group

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)

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

1. Willing to participate in the study and able to communicate consent during the consent process
2. Willing and able to complete all applicable Registry/Screening Visit assessments
3. Age ≥ 4 years
4. 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

OR

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:

1. Investigator confirms genotype and phenotype are consistent with autosomal recessive inheritance
2. The 2 disease-causing variants have not been reported in cis in variant databases
3. 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)
4. No potentially pathogenic variants were found in other common, likely candidate genes for the proposed condition

OR

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:

1. Both eyes must have a clinical diagnosis of retinal dystrophy
2. Both eyes must permit good quality photographic imaging (e.g., but not limited to, clear ocular media, adequate pupil dilation, stable fixation)

Exclusion Criteria

1\. 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.



1. Current vitreous hemorrhage
2. 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
3. History of intraocular surgery (for example, but not limited to, cataract surgery, vitrectomy, penetrating keratoplasty, or LASIK) within 3 months of Registry/Screening Visit
4. 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)
5. Current or any history of retinal vascular occlusion or proliferative diabetic retinopathy
6. 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)
7. 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
8. 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)
Minimum Eligible Age

4 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Foundation Fighting Blindness

OTHER

Sponsor Role collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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José-Alain Sahel, MD

Role: STUDY_CHAIR

Director, UPMC Eye Center University of Pittsburgh School of Medicine

Locations

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University of Arkansas, Jones Eye Institute

Little Rock, Arkansas, United States

Site Status RECRUITING

USC Roski Eye Institute

Los Angeles, California, United States

Site Status NOT_YET_RECRUITING

University of California San Francisco

San Francisco, California, United States

Site Status RECRUITING

University of Florida Health Jacksonville

Jacksonville, Florida, United States

Site Status RECRUITING

University of Miami, Bascom Palmer Eye Institute

Miami, Florida, United States

Site Status RECRUITING

Emory University, Emory Eye Center

Atlanta, Georgia, United States

Site Status RECRUITING

Johns Hopkins University, Wilmer Eye Institute

Baltimore, Maryland, United States

Site Status RECRUITING

Harvard Univ., Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan, Kellogg Eye Center

Ann Arbor, Michigan, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

Duke University, Duke Eye Center

Durham, North Carolina, United States

Site Status RECRUITING

Oregon Health & Science Univ., Casey Eye Institute

Portland, Oregon, United States

Site Status RECRUITING

University of Pennsylvania, Scheie Eye Institute

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

UPMC Eye Center

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Retina Foundation of the Southwest

Dallas, Texas, United States

Site Status RECRUITING

Baylor College of Medicine, Alkek Eye Center

Houston, Texas, United States

Site Status RECRUITING

University of Utah, John Moran Eye Center

Salt Lake City, Utah, United States

Site Status RECRUITING

University of Wisconsin Madison

Madison, Wisconsin, United States

Site Status RECRUITING

Medical College of Wisconsin Eye Institute

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Centre for Eye Research Australia

East Melbourne, Victoria, Australia

Site Status RECRUITING

Ghent University

Ghent, , Belgium

Site Status NOT_YET_RECRUITING

INRET Clínica e Centro de Pesquisa

Belo Horizonte, Minas Gerais, Brazil

Site Status RECRUITING

Instituto de Genética Ocular

São Paulo, São Paulo Province, Brazil

Site Status RECRUITING

University of Alberta and Alberta Health Services

Edmonton, Alberta, Canada

Site Status RECRUITING

University of Toronto, Hospital for Sick Children

Toronto, Ontario, Canada

Site Status RECRUITING

University Health Network

Toronto, , Canada

Site Status RECRUITING

Helsinki University Hospital

Helsinki, , Finland

Site Status RECRUITING

CHNO des Quinze-Vingts

Paris, , France

Site Status RECRUITING

Hadassah-Hebrew University Medical Center

Jerusalem, , Israel

Site Status RECRUITING

Vista Vision Eye Clinic

Brescia, , Italy

Site Status RECRUITING

Retina and Genomics Institute

Yucatán, Merida, Mexico

Site Status RECRUITING

Radboud University Medical Center

Nijmegen, , Netherlands

Site Status RECRUITING

Oslo University Hospital

Oslo, , Norway

Site Status NOT_YET_RECRUITING

University Hospital Basel

Basel, Canton of Basel-City, Switzerland

Site Status RECRUITING

University Hospital Jules-Gonin

Lausanne, , Switzerland

Site Status RECRUITING

Moorfields Eye Hospital

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Belgium Brazil Canada Finland France Israel Italy Mexico Netherlands Norway Switzerland United Kingdom

Central Contacts

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Coordinating Center

Role: CONTACT

813-975-8690

Facility Contacts

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Sami Uwaydat, MD

Role: primary

501-296-1156

Hossein Ameri, MD, PhD

Role: primary

323-442-6490

Jacque Duncan, MD

Role: primary

415-502-5161

Sandeep Grover, MD

Role: primary

Byron Lam, MD

Role: primary

305-482-5121

Nieraj Jain, MD

Role: primary

404-778-4725

Mandeep S. Singh, MD, PhD

Role: primary

443-287-7912

Role: backup

410-502-1231

Rachel Huckfeldt, MD, PhD

Role: primary

617-573-4401

Abigail Fahim, MD, PhD

Role: primary

734-615-8560

Brittni Scruggs, MD, PhD

Role: primary

507-538-8119

Ramiro Maldonado, MD

Role: primary

919-668-8333

Lesley Everett, MD, PhD

Role: primary

503-494-3370

Tomas Aleman, MD

Role: primary

215-662-6396

Boris Rosin, MD, PhD

Role: primary

412-642-1940

Mark Pennesi, PhD

Role: primary

214-363-3911

Kaylie Jones

Role: backup

John T. Stout, MD, PhD

Role: primary

713-798-2759

Paul Bernstein, MD, PhD

Role: primary

801-213-2034

Kimberly Stepien, MD

Role: primary

608-263-8783

Thomas Connor, MD

Role: primary

414-955-2001

Lauren Ayton, MD, PhD

Role: primary

61 3 8344 3441

Bart Leroy, MD, PhD

Role: primary

Fernanda Belga Ottoni Porto, MD, PhD

Role: primary

55 31 32264882

Juliana Sallum, MD, PhD

Role: primary

55 11 98346 ext. 3053

Ian MacDonald, MSc, MD CM

Role: primary

780 492 8869

Elise Heon, MD

Role: primary

416.813.7654 ext. 301511

Sabahat Javaid

Role: backup

Brian Ballios, MD, PhD

Role: primary

416-603-5800 ext. 3106

Eeva-Marja Sankila, MD

Role: primary

+358 9 4711

Isabelle Audo, MD

Role: primary

+33(0) 1 40 02 14 55

Eyal Banin, MD

Role: primary

972-54-4969153

Giacomo Calzetti, MD

Role: primary

39 333 932 9837

Adda Villanueva, MD

Role: primary

52 999 22 33 623

Role: backup

52 999 406 0586

Suzanna Yzer, MD

Role: primary

+31 24 3613212

Josephine P Holtan, MD, PhD

Role: primary

Nicolas Feltgen, MD

Role: primary

41 79 172 92 48

Hoai V. Tran, MD

Role: primary

+41 (0)21 626 8154

Michel Michaelides, MD

Role: primary

02075662108

Provided Documents

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Document Type: Study Protocol

View Document

Related Links

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https://public.jaeb.org/ffb

Foundation Fighting Blindness Public Website

Other Identifiers

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Uni-Rare

Identifier Type: -

Identifier Source: org_study_id

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