Rate of Progression in USH2A-related Retinal Degeneration

NCT03146078 | Active Not Recruiting DMC

• 1 other identifier: RUSH2A
• Study Type: observational
• Target: 127
• Locations: 6 countries
• Sites: 14

Brief Summary

The overall goal of this project funded by the Foundation Fighting Blindness is to characterize the natural history of disease progression in patients with USH2A related retinal degeneration associated with congenital hearing loss (Usher syndrome type 2a) or non-syndromic retinitis pigmentosa (RP39). RUSH2A Extension Study: The purpose of this addendum is to extend RUSH2A to 7- and 9-year visits, with the goal to use longer term data to further develop and support early candidate endpoints as possible clinical trial outcomes.

Conditions

Usher Syndrome, Type 2A; Retinitis Pigmentosa 39

Outcome Measures

Primary Outcomes (6)

• Characterize Change using Visual Field Sensitivity

  Measured by static perimetry with topographic analysis (Hill of Vision)

  Baseline and every year until study completion (4 years)

• Characterize Change using Visual Acuity

  Best corrected E-ETDRS visual acuity

  Baseline and every year until study completion (4 years)

• Characterize Change using Mean Retinal Sensitivity

  Measured by fundus-guided microperimetry

  Baseline and every year until study completion (4 years)

• Characterize Change in EZ area

  Measured by SD-OCT

  Baseline and every year until study completion (4 years)

• Characterize Change in Rod- and cone-mediated retinal function

  Measured by FST

  Baseline and every year until study completion (4 years)

• Characterize Change in Retinal function

  Full-field ERG amplitudes and timing in response to rod- and cone-specific stimuli

  Baseline and after four years

Secondary Outcomes (1)

• MOST-VR Mobility Testing

  Seven and nine year visits

Study Arms (3)

Primary Cohort

Participants with baseline visual acuity ETDRS letter score of 54 or more \[approximate Snellen equivalent 20/80 or better\] and stable fixation and clinically determined \[on Octopus 900 Pro\] kinetic visual field III4e area 10° or more in the study eye ("primary cohort") will be enrolled into the longitudinal natural history study

Secondary Cohort

Participants with baseline visual acuity ETDRS letter score of 53 or less \[approximate Snellen equivalent 20/100 or worse\] or unstable fixation or clinically determined \[on Octopus 900 Pro\] kinetic visual field III4e area less than 10°in the study eye ("secondary cohort") will be enrolled in the cross-sectional baseline study

Virtual Reality (VR) Cohort

A subset of sites participating in the VR ancillary study will complete a feasibility questionnaire, including assessment of available space for running the testing procedures. Selected sites will work with VR vendor to complete installation, training, and certification requirements. Eligible participants will be presented with the opportunity to participate in the RUSH2A Extension Study at sites participating in the VR Ancillary Study. Participants at VR Sites must consent to the VR Ancillary Study to participate in the RUSH2A Extension Study.

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

Potential eligibility will be assessed during a routine examination by an investigator prior to obtaining informed consent, as part of usual care

You may qualify if:

• Willing and able to complete the informed consent process
• Ability to return for all study visits over 48 months if in the natural history study
• Age ≥ 8 years
• At least 2 pathogenic or likely pathogenic mutations in USH2A gene from a clinically certified lab report
• Both eyes must meet all of the following:
• Clinical diagnosis of a rod-cone degeneration
• Clear ocular media and adequate pupil dilation to permit good quality photographic imaging
• Ability to perform kinetic and static perimetry reliably

You may not qualify if:

• Mutations in genes that cause autosomal dominant RP, X-linked RP, or presence of biallelic mutations in autosomal recessive RP/retinal dystrophy genes other than USH2A
• 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)
• If either eye has any of the following, the patient is not eligible:
• Current vitreous hemorrhage
• Current or any history of 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 glaucoma visual field, nerve changes, or glaucoma filtering surgery)
• Current or any history of retinal vascular occlusion or proliferative diabetic retinopathy
• Expected to have cataract removal surgery during the study
• History or current evidence of ocular disease that, in the opinion of the investigator, may confound assessment of visual function
• History of treatment for retinitis pigmentosa that could affect the progression of retinal degeneration (including participation in a clinical trial within the last year or a retained drug delivery device)

Sponsors & Collaborators

• Jaeb Center for Health Research: lead
• Foundation Fighting Blindness: collaborator

Study Sites (14)

University of California, San Francisco

San Francisco, California, 94143-0344, United States

Location

Vitreo-Retinal Associates

Gainesville, Florida, 32607, United States

Location

Wilmer Eye Institute at Johns Hopkins

Baltimore, Maryland, 21287-9277, United States

Location

Massachusetts Eye and Ear

Boston, Massachusetts, 02114, United States

Location

Kellogg Eye Center, University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

OHSU Casey Eye Institute

Portland, Oregon, 97239, United States

Location

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

Location

Baylor Eye Physicians and Surgeons

Houston, Texas, 77030, United States

Location

Moran Eye Center, University of Utah

Salt Lake City, Utah, 84107, United States

Location

Hospital for Sick Children

Toronto, Canada

Location

Centre hospitalier National d'Ophtalmologie des Quinze-Vingts

Paris, 75012, France

Location

University of Tubingen

Tübingen, Germany

Location

Radboud University

Nijmegen, Netherlands

Location

Moorfields Eye Hospital

London, United Kingdom

Location

Related Links

• public website

Biospecimen

Retention: SAMPLES WITH DNA

Saliva samples

MeSH Terms

Conditions

Usher syndrome, type 2A

Study Officials

• Jacque Duncan, MD

  University of California, San Francisco

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: May 4, 2017
• First Posted: May 9, 2017
• Study Start: August 11, 2017
• Primary Completion: April 28, 2023
• Study Completion (Estimated): December 1, 2029
• Last Updated: February 4, 2026

Record last verified: 2025-06

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

GB (1); NL (1); US (9); FR (1); CA (1); DE (1)