Retinal DegenerationRUSH1FNCT04765345
Rate of Progression of PCDH15-Related Retinal Degeneration in Usher Syndrome 1F
An observational study of Retinal Degeneration and Retinitis Pigmentosa, run by Jaeb Center for Health Research at 10 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 8 years and older
- Conditions the study is for
- Retinal Degeneration, Retinitis Pigmentosa, Eye Diseases, Hereditary
- How many people
- 44 participants
- Where
- 10 sitesin 8 countries
- Study dates
- 8 Jun 2021to 30 Jun 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- Participants must meet all the following inclusion criteria at the Screening Visit in order to be eligible to enroll into the genetic screening phase.
- 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:
Show all 14Show fewer
- 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.
- Clinical diagnosis of retinal dystrophy
- Clear ocular media and adequate pupil dilation to permit good quality photographic imaging
Who cannot join
- Participants must not meet any of the following exclusion criteria at the Screening Visit in order to be eligible to enroll into the genetic screening phase.
- 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.
- Ocular Exclusion Criteria
Show all 20Show fewer
- 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
- Treatment with an ophthalmic oligonucleotide within the last 9 months (last treatment date is less than 9 months prior to Screening Visit date)
- Treatment with any other product within five times the expected half-life of the product (time from last treatment date to Screening Visit date is at least 5 times the half-life of the given product)
- Treatment with Ozurdex (dexamethasone), Iluvien or Yutiq (fluocinolone acetonide) intravitreal implant
Trial locations and contacts
10 sites in 8 countries.
10 sites in 8 countries
United States3 sites
The Johns Hopkins Wilmer Eye Institute
Baltimore, Maryland, 21287
Duke University, Duke Eye Center
Durham, North Carolina, 27710
University of California, San Francisco
San Francisco, California, 94143-0344
About this study
Official title: Rate of Progression of PCDH15-Related Retinal Degeneration in Usher
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.
Read the 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:
- Describe the natural history of retinal degeneration in patients with biallelic disease-causing variants in the PCDH15 gene
- Contribute to the identification of sensitive structural and functional outcome measures to use for future multicenter clinical trials in PCDH15 related retinal degeneration
- 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:
- 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
- Explore whether structural outcome measures can be validated as surrogates for functional outcomes in individuals with biallelic pathogenic mutations in the PCDH15 gene
- 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
- Explore variability and symmetry of left and right eye outcomes over 4 years in individuals with biallelic pathogenic mutations in the PCDH15 gene
- Keywords
- PCDH15
- Medical subject headings
- Retinal Degeneration, Retinitis Pigmentosa, Eye Diseases, Hereditary, Deafness, Autosomal Recessive 23
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Visual Field Sensitivity
measured by static perimetry with quantitative, topographic analysis (Hill of Vision) and assessed by a central reading center
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.)
Measured: Screening, Baseline, 12Month, 24Month, 36Month, and 48Month
Change in Contrast Sensitivity Function (CSF)
Measured by the CSV-1000E VectorVision chart
Measured: 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.
Measured: Baseline, 12Month, 24Month, 36Month, and 48Month
Secondary outcomes (2)
Explore qualitative categorization of Fundus Autofluorescence (FAF) pattern
Assessed by a central reading center.
Measured: Baseline, 12Month, 24Month, 36Month, and 48Month
Explore quantitative measures of FAF
Assessed by a central reading center.
Measured: Baseline, 12Month, 24Month, 36Month, and 48Month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start8 Jun 2021
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Retinal DegenerationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jaeb Center for Health Research
- Sponsor type
- University, hospital or other
- Collaborators
- Usher 1F Collaborative, Marjorie C. Adams Foundation, Foundation Fighting Blindness
- Responsible party
- Sponsor
- Investigators
- Katarina Stingl, MD, Study chair, University Hospital Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04765345
- Sponsor's protocol ID
- RUSH1F
- Acronym
- RUSH1F
- Status last verified
- Jan 2026
- First submitted
- 2 Feb 2021
- Last updated
- 4 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: A de-identified database is placed in the public domain on the FFB/Jaeb public website after the completion of each protocol and publication of the manuscript.
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rate of Progression of PCDH15-Related Retinal Degeneration in Usher
- ClinicalTrials.gov ID
- NCT04765345
- Acronym / sponsor ID
- RUSH1F / RUSH1F
- Keywords
- PCDH15
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Jaeb Center for Health ResearchUniversity, hospital or other
- Collaborators
- Usher 1F Collaborative, Marjorie C. Adams Foundation, Foundation Fighting Blindness
- Study start
- 8 Jun 2021 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 21 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Describe the natural history of retinal degeneration in patients with biallelic disease-causing variants in the PCDH15 gene
- Contribute to the identification of sensitive structural and functional outcome measures to use for future multicenter clinical trials in PCDH15 related retinal degeneration
- 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:
- 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
- Explore whether structural outcome measures can be validated as surrogates for functional outcomes in individuals with biallelic pathogenic mutations in the PCDH15 gene
- 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
- Explore variability and symmetry of left and right eye outcomes over 4 years in individuals with biallelic pathogenic mutations in the PCDH15 gene
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (14 listed)
- Participants must meet all the following inclusion criteria at the Screening Visit in order to be eligible to enroll into the genetic screening phase.
- 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
Key exclusion criteria (20 listed)
- Participants must not meet any of the following exclusion criteria at the Screening Visit in order to be eligible to enroll into the genetic screening phase.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in Visual Field Sensitivity
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: Baseline, 12Month, 24Month, 36Month, and 48Month
Measured by the CSV-1000E VectorVision chart
Change in ellipsoid zone (EZ) area
Time frame: Baseline, 12Month, 24Month, 36Month, and 48Month
Measured by spectral domain optical coherence tomography (SD-OCT) and assessed by a central reading center.
2 secondary outcomes
Explore qualitative categorization of Fundus Autofluorescence (FAF) pattern
Time frame: Baseline, 12Month, 24Month, 36Month, and 48Month
Explore quantitative measures of FAF
Time frame: Baseline, 12Month, 24Month, 36Month, and 48Month
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2026.
- Foundation Fighting Blindness Public WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. A de-identified database is placed in the public domain on the FFB/Jaeb public website after the completion of each protocol and publication of the manuscript.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katarina Stingl, MD study chair
University Hospital Tuebingen
10 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Retinal Degeneration and Retinitis Pigmentosa, run by Jaeb Center for Health Research at 10 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Canada, France, Germany, Israel and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Visual Field Sensitivity (time frame: 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). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2026.