Eye Diseases, Hereditary, Retinal Degeneration, Retinitis Pigmentosa
Conditions
Keywords
PCDH15
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.
Detailed description
This natural history study of patients with PCDH15 disease-causing variants will accelerate the development of outcome measures for clinical trials. Sensitive, reliable outcome measures of retinal degeneration will greatly facilitate development of treatments for retinitis pigmentosa due to PCDH15 disease-causing variants. Together these approaches are expected to have an impact on understanding PCDH15 related retinal degeneration, developing experimental treatment protocols, and assessing their effectiveness. The goals and expected impact of this natural history study are to: 1. Describe the natural history of retinal degeneration in patients with biallelic disease-causing variants in the PCDH15 gene 2. Contribute to the identification of sensitive structural and functional outcome measures to use for future multicenter clinical trials in PCDH15 related retinal degeneration 3. Contribute to the identification of populations for future clinical trials of investigative treatments for PCDH15 related retinal degeneration Study Objectives The primary objectives of the natural history study are to: 1. Characterize the natural history of retinal degeneration associated with biallelic pathogenic mutations in the PCDH15gene over 4 years, as measured using functional, structural, and patient-reported outcome measures 2. Explore whether structural outcome measures can be validated as surrogates for functional outcomes in individuals with biallelic pathogenic mutations in the PCDH15 gene 3. Explore possible risk factors (genotype, phenotype, environmental, and comorbidities) for progression of the outcome measures at 4 years in individuals with biallelic pathogenic mutations in the PCDH15 gene 4. Explore variability and symmetry of left and right eye outcomes over 4 years in individuals with biallelic pathogenic mutations in the PCDH15 gene
Interventions
None listed
Sponsors
Jaeb Center for Health Research
Usher 1F Collaborative
Marjorie C. Adams Foundation
Foundation Fighting Blindness
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
8 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants must meet all the following inclusion criteria at the Screening Visit in order 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. Ability to return for all study visits over 48 months 3. Age ≥ 8 years 4. Not planning to enroll in an experimental clinical trial for the treatment of PCDH15 for the duration of this study 5. 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. Ocular Inclusion Criteria Both eyes must meet all the following at the Screening Visit for a participant to be eligible to enroll into the genetic screening phase. 1. Clinical diagnosis of retinal dystrophy 2. Clear ocular media and adequate pupil dilation to permit good quality photographic imaging
Exclusion criteria
Participants must not meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visual Field Sensitivity | 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 | measured by static perimetry with quantitative, topographic analysis (Hill of Vision) and assessed by a central reading center |
| Change in Best Corrected Visual Acuity | Screening, Baseline, 12Month, 24Month, 36Month, and 48Month | 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. |
| Change in Mean Retinal Sensitivity | 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 | Measured by fundus-guided microperimetry (MP) and assessed by a central reading center at selected sites with requisite equipment. |
| Change in Full-field Retinal Sensitivity | Baseline, 12Month, 24Month, 36Month, and 48Month | Measured by full-field stimulus threshold (FST) testing to blue, white and red stimuli. |
| Change in Best Corrected Low Luminance Visual Acuity (LLVA) | Screening, Baseline, 12Month, 24Month, 36Month, and 48Month | Measured by Letter Score. Letter score range values=0-100 (with higher values = better and lower values = worse.) |
| Change in Contrast Sensitivity Function (CSF) | Baseline, 12Month, 24Month, 36Month, and 48Month | Measured by the CSV-1000E VectorVision chart |
| Change in ellipsoid zone (EZ) area | Baseline, 12Month, 24Month, 36Month, and 48Month | Measured by spectral domain optical coherence tomography (SD-OCT) and assessed by a central reading center. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Explore qualitative categorization of Fundus Autofluorescence (FAF) pattern | Baseline, 12Month, 24Month, 36Month, and 48Month | Assessed by a central reading center. |
| Explore quantitative measures of FAF | Baseline, 12Month, 24Month, 36Month, and 48Month | Assessed by a central reading center. |
Countries
Canada, France, Germany, Israel, Netherlands, Switzerland, United Kingdom, United States
Contacts
STUDY_CHAIRKatarina Stingl, MD
University Hospital Tuebingen
Outcome results
None listed