Registry and natural history study of retinal dystrophies linked to rare genetic variants

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

This study is trying to track how inherited eye conditions linked to rare genetic changes affect people over time, while also creating a registry to help understand these conditions better.

Quick facts

• Study type: Observational
• Enrollment: 1500 (estimated)
• Ages: 4 Years and up
• Sex: All
• Sponsor: Jaeb Center for Health Research (other)
• Locations: 36 sites (Little Rock, Arkansas and 35 other locations)
• Trial ID: NCT05589714 on ClinicalTrials.gov

What this trial studies

This international, multicenter study aims to create a registry and conduct a natural history study for patients with inherited retinal degeneration associated with rare genetic variants. It involves standardized genetic screening and clinical data collection, focusing on genotype and phenotype characterization. Participants will be enrolled based on their genetic reports, and the study will track the progression of their conditions over time. The study also aims to establish a link to the My Retina Tracker Registry and conduct ancillary exploratory studies.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 4 years and older with a confirmed genetic variant on the RD Rare Gene List.

Not a fit: Patients without a genetic variant on the RD Rare Gene List or those who do not meet the genetic screening criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance understanding of retinal dystrophies and improve patient management and treatment options.

How similar studies have performed: Other studies focusing on genetic registries and natural history have shown promise in understanding rare diseases, making this approach both relevant and potentially impactful.

Eligibility criteria

Inclusion Criteria: Participants must meet all the following inclusion criteria at the Registry/Screening Visit to be eligible to enroll into the genetic screening phase:

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:

Participants must not meet any of the following exclusion criteria at the Registry/Screening Visit to be eligible to enroll into the genetic screening phase:

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.

Ocular Exclusion Criteria:

If either eye has any of the following ocular exclusion criteria at the Registry/Screening Visit, then the participant is not eligible to enroll into the genetic screening phase:

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)

Where this trial is running

Little Rock, Arkansas and 35 other locations

• University of Arkansas, Jones Eye Institute — Little Rock, Arkansas, United States (RECRUITING)
• USC Roski Eye Institute — Los Angeles, California, United States (NOT_YET_RECRUITING)
• University of California San Francisco — San Francisco, California, United States (RECRUITING)
• University of Florida Health Jacksonville — Jacksonville, Florida, United States (RECRUITING)
• University of Miami, Bascom Palmer Eye Institute — Miami, Florida, United States (RECRUITING)
• Emory University, Emory Eye Center — Atlanta, Georgia, United States (RECRUITING)
• Johns Hopkins University, Wilmer Eye Institute — Baltimore, Maryland, United States (RECRUITING)
• Harvard Univ., Massachusetts Eye and Ear Infirmary — Boston, Massachusetts, United States (RECRUITING)
• University of Michigan, Kellogg Eye Center — Ann Arbor, Michigan, United States (RECRUITING)
• Mayo Clinic — Rochester, Minnesota, United States (RECRUITING)
• Duke University, Duke Eye Center — Durham, North Carolina, United States (RECRUITING)
• Oregon Health & Science Univ., Casey Eye Institute — Portland, Oregon, United States (RECRUITING)
• University of Pennsylvania, Scheie Eye Institute — Philadelphia, Pennsylvania, United States (RECRUITING)
• UPMC Eye Center — Pittsburgh, Pennsylvania, United States (RECRUITING)
• Retina Foundation of the Southwest — Dallas, Texas, United States (RECRUITING)
• Baylor College of Medicine, Alkek Eye Center — Houston, Texas, United States (RECRUITING)
• University of Utah, John Moran Eye Center — Salt Lake City, Utah, United States (RECRUITING)
• University of Wisconsin Madison — Madison, Wisconsin, United States (RECRUITING)
• Medical College of Wisconsin Eye Institute — Milwaukee, Wisconsin, 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, 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, Canada (RECRUITING)
• University Health Network — Toronto, Canada (RECRUITING)
• Helsinki University Hospital — Helsinki, Finland (RECRUITING)
• CHNO des Quinze-Vingts — Paris, France (RECRUITING)
• Hadassah-Hebrew University Medical Center — Jerusalem, Israel (RECRUITING)
• Vista Vision Eye Clinic — Brescia, Italy (RECRUITING)
• Retina and Genomics Institute — Yucatán, Merida, Mexico (RECRUITING)
• Radboud University Medical Center — Nijmegen, 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, Switzerland (RECRUITING)
• Moorfields Eye Hospital — London, United Kingdom (RECRUITING)

Study contacts

• Study coordinator: Coordinating Center

Conditions: Inherited Retinal Degeneration, Retinitis Pigmentosa