Rate of Progression of PCDH15-Related Retinal Degeneration in Usher Syndrome 1F

NCT04765345 | Active Not Recruiting DMC

• 1 other identifier: RUSH1F
• Study Type: observational
• Target: 44
• Locations: 8 countries
• Sites: 10

Brief Summary

The overall goal of this project, co-funded by the Foundation Fighting Blindness and the USHER 1F Collaborative is to characterize the natural history of disease progression in patients with PCDH15 mutations in order to accelerate the development of outcome measures for clinical trials.

Conditions

Retinal Degeneration; Retinitis Pigmentosa; Eye Diseases, Hereditary

Keywords

PCDH15

Outcome Measures

Primary Outcomes (7)

• Change in Visual Field Sensitivity

  measured by static perimetry with quantitative, topographic analysis (Hill of Vision) and assessed by a central reading center

  Baseline (all Vision Cohort 1 and 2 participants will complete two tests at baseline. The results will be compared according to the visual field criteria to determine if a third test is needed), 12Month, 24Month, 36Month, and 48Month

• Change in Best Corrected Visual Acuity

  Early Treatment of Diabetic Retinopathy Study (ETDRS) Best corrected visual acuity (BCVA) letter score as measured on the Electronic Visual Acuity (EVA) system or ETDRS charts. Letter score range values=0-100 (with higher values = better and lower values = worse.) Berkeley Rudimentary Vision Test (BRVT) will be used for patients unable to see letters.

  Screening, Baseline, 12Month, 24Month, 36Month, and 48Month

• Change in Mean Retinal Sensitivity

  Measured by fundus-guided microperimetry (MP) and assessed by a central reading center at selected sites with requisite equipment.

  Baseline (all Vision Cohort 1 and 2 participants will complete two tests at baseline. The results will be compared according to the visual field criteria to determine if a third test is needed), 12Month, 24Month, 36Month, and 48Month

• Change in Full-field Retinal Sensitivity

  Measured by full-field stimulus threshold (FST) testing to blue, white and red stimuli.

  Baseline, 12Month, 24Month, 36Month, and 48Month

• Change in Best Corrected Low Luminance Visual Acuity (LLVA)

  Measured by Letter Score. Letter score range values=0-100 (with higher values = better and lower values = worse.)

  Screening, Baseline, 12Month, 24Month, 36Month, and 48Month

• Change in Contrast Sensitivity Function (CSF)

  Measured by the CSV-1000E VectorVision chart

  Baseline, 12Month, 24Month, 36Month, and 48Month

• Change in ellipsoid zone (EZ) area

  Measured by spectral domain optical coherence tomography (SD-OCT) and assessed by a central reading center.

  Baseline, 12Month, 24Month, 36Month, and 48Month

Secondary Outcomes (2)

• Explore qualitative categorization of Fundus Autofluorescence (FAF) pattern

  Baseline, 12Month, 24Month, 36Month, and 48Month

• Explore quantitative measures of FAF

  Baseline, 12Month, 24Month, 36Month, and 48Month

Other Outcomes (3)

• Patient Reported Outcomes (Adults 18 years or older)

  Baseline, 24Month, and 48Month

• Patient Reported Outcomes (Adults 18 years or older)

  Baseline, 24Month, and 48Month

• Patient Reported Outcomes (less than 18 years):

  Baseline, 24Month, and 48Month

Study Arms (2)

Vision Cohort 1

\~25 participants with the better eye 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. The better eye is defined as the eye with better Screening Visit ETDRS VA. If both eyes have the same VA (defined as the same Snellen equivalent), then the determination will be made at investigator discretion as the eye with better fixation or clearer ocular media to permit highest quality retinal imaging. The visual field (VF) is defined as the clinically determined kinetic VF III4e performed within the last 18 months prior to or including the Screening Visit date.

Vision Cohort 2

\~15 participants with the better eye Screening Visit visual acuity ETDRS letter score of 19-53 \[approximate Snellen equivalent 20/100 - 20/400\] 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). The better eye is defined as the eye with better Screening Visit ETDRS VA. If both eyes have the same VA (defined as the same Snellen equivalent), then the determination will be made at investigator discretion as the eye with better fixation or clearer ocular media to permit highest quality retinal imaging. The visual field (VF) is defined as the clinically determined kinetic VF III4e performed within the last 18 months prior to or including the Screening Visit date.

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study participants will be recruited from approximately 10 clinical sites worldwide. All eligible participants will be included without regard to gender, race, or ethnicity. Potential eligibility will be assessed during a routine examination by an investigator prior to obtaining informed consent, as part of usual care, through referrals from other providers or self-referral.

You may qualify if:

• Willing to participate in the study and able to communicate consent during the consent process
• Ability to return for all study visits over 48 months
• Age ≥ 8 years
• Not planning to enroll in an experimental clinical trial for the treatment of PCDH15 for the duration of this study
• Must meet one of the Genetic Screening Criteria, defined below:
• Screening Group A: At least 2 disease-causing variants in the PCDH15 gene which are homozygous or heterozygous in trans, based on a report from a clinically certified lab (or a report from a research lab that has been pre- approved by the Genetics Committee)
• Screening Group B: Only 1 disease-causing variant in the PCDH15 gene, based on a report from a clinically certified lab (or a report from a research lab which has been pre-approved by the Genetics Committee)
• Screening Group C: At least 2 disease-causing variants in the PCDH15 gene which are unknown phase, based on a report from a clinically certified lab (or a report from a research lab which has been pre-approved by the Genetics Committee)
• Note pertaining to all Screening Groups: if a participant has a variant(s) of unknown significance, he/she would still qualify if there is at least 1 disease-causing variant(s) on the PCDH15 gene. The Genetics Committee will review unique cases where segregation analysis is not feasible to determine eligibility.
• Both eyes must meet all the following at the Screening Visit for a participant to be eligible to enroll into the genetic screening phase.
• Clinical diagnosis of retinal dystrophy
• Clear ocular media and adequate pupil dilation to permit good quality photographic imaging

You may not qualify if:

• Mutations in genes that cause autosomal dominant retinitis pigmentosa (ADRP), X-linked retinitis pigmentosa (RP), or presence of biallelic mutations in autosomal recessive RP/retinal dystrophy genes other than PCDH15
• Expected to enter experimental treatment trial at any time during this study
• History of more than 1 year of cumulative treatment, at any time, with an agent associated with pigmentary retinopathy (including hydroxychloroquine, chloroquine, thioridazine, and deferoxamine)
• Note: Pregnant women are not being specifically excluded from participation.
• If either eye has any of the following at the Screening Visit, the participant is not eligible to enroll into the genetic screening phase.
• Current vitreous hemorrhage
• Current or any history of tractional or rhegmatogenous retinal detachment
• Current or any history of (e.g., prior to cataract or refractive surgery) spherical equivalent of the refractive error worse than -8 Diopters of myopia
• History of intraocular surgery (e.g., cataract surgery, vitrectomy, penetrating keratoplasty, or LASIK) within the last 3 months
• Current or any history of confirmed diagnosis of glaucoma (e.g., based on 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
• History or evidence of active treatment for retinitis pigmentosa that could affect the progression of retinal degeneration, including:
• Any use of ocular stem cell or gene therapy
• Any treatment with ocriplasmin

Sponsors & Collaborators

• Jaeb Center for Health Research: lead
• Usher 1F Collaborative: collaborator
• Marjorie C. Adams Foundation: collaborator
• Foundation Fighting Blindness: collaborator

Study Sites (10)

University of California, San Francisco

San Francisco, California, 94143-0344, United States

Location

The Johns Hopkins Wilmer Eye Institute

Baltimore, Maryland, 21287, United States

Location

Duke University, Duke Eye Center

Durham, North Carolina, 27710, United States

Location

Hospital for Sick Children

Toronto, Ontario, Canada

Location

CHNO des Quinze-Vingts

Paris, France

Location

University of Tubingen

Tübingen, Germany

Location

Haddassah Medical Center

Jerusalem, Israel

Location

Radboud University

Nijmegen, Netherlands

Location

University Hospital Basel

Basel, 4031, Switzerland

Location

Moorfields Eye Hospital

London, EC1V 2PD, United Kingdom

Location

Related Links

• Foundation Fighting Blindness Public Website

Biospecimen

Retention: SAMPLES WITH DNA

Saliva samples

MeSH Terms

Conditions

Retinal Degeneration; Retinitis Pigmentosa; Eye Diseases, Hereditary; Deafness, Autosomal Recessive 23

Condition Hierarchy (Ancestors)

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

Study Officials

• Katarina Stingl, MD

  University Hospital Tuebingen

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: February 2, 2021
• First Posted: February 21, 2021
• Study Start: June 8, 2021
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: February 4, 2026

Record last verified: 2026-01

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

CA (1); US (3); NL (1); CH (1); FR (1); IL (1); DE (1); GB (1)