Rate of Progression in USH2A-related Retinal Degeneration
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 127
- Locations
- 14
- Primary Endpoint
- Characterize Change using Mean Retinal Sensitivity
Study Overview
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.
Detailed Description
This natural history study of patients with USH2A mutations will accelerate the development of outcome measures for clinical trials. Sensitive, objective outcome measures of retinal degeneration will greatly facilitate development of treatments for Usher syndrome patients. Together these approaches are expected to have an impact on understanding USH2A-related retinal degeneration, developing experimental treatment protocols, and assessing their effectiveness.
The goals and expected impact of this natural history study are to:
- Report the natural history of retinal degeneration in patients with biallelic mutations in the USH2A gene
- Identify sensitive structural and functional outcome measures to use for future multicenter clinical trials in USH2A-related retinal degeneration
- Identify well-defined subpopulations for future clinical trials of investigative treatments for USH2A-related retinal degeneration
Study Objectives
The primary objectives of the natural history study are to:
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 8 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •Ocular Inclusion Criteria
- •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
Exclusion Criteria
- •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)
- •Ocular Exclusion Criteria
- •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)
Arms & Interventions
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.
Outcomes
Primary Outcomes
Characterize Change using Mean Retinal Sensitivity
Time Frame: Baseline and every year until study completion (4 years)
Measured by fundus-guided microperimetry
Characterize Change in Rod- and cone-mediated retinal function
Time Frame: Baseline and every year until study completion (4 years)
Measured by FST
Characterize Change using Visual Field Sensitivity
Time Frame: Baseline and every year until study completion (4 years)
Measured by static perimetry with topographic analysis (Hill of Vision)
Characterize Change in Retinal function
Time Frame: Baseline and after four years
Full-field ERG amplitudes and timing in response to rod- and cone-specific stimuli
Characterize Change using Visual Acuity
Time Frame: Baseline and every year until study completion (4 years)
Best corrected E-ETDRS visual acuity
Characterize Change in EZ area
Time Frame: Baseline and every year until study completion (4 years)
Measured by SD-OCT
Secondary Outcomes
- MOST-VR Mobility Testing(Seven and nine year visits)