Rate of Progression in USH2A-related Retinal Degeneration

Usher Syndrome, Type 2A Clinical Trial

— RUSH2A  

Official title:

Rate of Progression in USH2A-related Retinal Degeneration

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03146078
• Other study ID #: RUSH2A
• Status: Active, not recruiting
• Start date: August 11, 2017
• Est. completion date: December 2029

Study information

• Verified date: April 2024
• Source: Jaeb Center for Health Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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:

1. Report the natural history of retinal degeneration in patients with biallelic mutations in the USH2A gene

2. Identify sensitive structural and functional outcome measures to use for future multicenter clinical trials in USH2A-related retinal degeneration

3. 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:

1. Characterize the natural history of retinal degeneration associated with biallelic pathogenic mutations in the USH2A gene over 4 years, as measured using functional outcome measures (static perimetry, microperimetry, full-field stimulus threshold (FST), electroretinography (ERG), and visual acuity)

2. Characterize the natural history of retinal degeneration associated with biallelic pathogenic mutations in the USH2A gene over 4 years, as measured using structural outcome measures (spectral-domain optical coherence tomography (SD-OCT) ellipsoid zone (EZ) area)

3. Investigate structure-function relationships for insights into the mechanisms of retinal degeneration by relating changes in SD-OCT EZ area to visual field progression in individuals with biallelic pathogenic mutations in the USH2A gene

4. Assess for possible genotype, phenotype, and environmental risk factors with progression of the outcome measures at 4 years in individuals with biallelic pathogenic mutations in the USH2A gene

Some additional secondary objectives of this study include:

1. Characterize baseline cross-sectional retinal degeneration associated with biallelic pathogenic mutations in the USH2A gene (as measured using the main outcome measures)

2. Investigate comorbidities associated with disease (baseline cross-sectional) and disease progression (longitudinal natural history study) in individuals with biallelic pathogenic mutations in the USH2A gene

3. Explore patient reported outcome (PRO) measures associated with disease (baseline cross-sectional) and disease progression (longitudinal natural history study) in individuals with biallelic pathogenic mutations in the USH2A gene

4. Evaluate variability and symmetry of left and right eye kinetic perimetry and SD-OCT outcomes at baseline and at 4 years in individuals with biallelic pathogenic mutations in the USH2A gene

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 127
• Est. completion date: December 2029
• Est. primary completion date: April 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Retinal Degeneration
• Retinitis
• Retinitis Pigmentosa
• Retinitis Pigmentosa 39
• Usher Syndrome, Type 2A
• Usher Syndromes

Locations

Country	Name	City	State
Canada	Hospital for Sick Children	Toronto
France	Centre hospitalier National d'Ophtalmologie des Quinze-Vingts	Paris
Germany	University of Tubingen	Tübingen
Netherlands	Radboud University	Nijmegen
United Kingdom	Moorfields Eye Hospital	London
United States	Kellogg Eye Center, University of Michigan	Ann Arbor	Michigan
United States	Wilmer Eye Institute at Johns Hopkins	Baltimore	Maryland
United States	Massachusetts Eye and Ear	Boston	Massachusetts
United States	Retina Foundation of the Southwest	Dallas	Texas
United States	Duke University Eye Center	Durham	North Carolina
United States	Vitreo-Retinal Associates	Gainesville	Florida
United States	Baylor Eye Physicians and Surgeons	Houston	Texas
United States	Medical College of Wiconsin	Milwaukee	Wisconsin
United States	OHSU Casey Eye Institute	Portland	Oregon
United States	Moran Eye Center, University of Utah	Salt Lake City	Utah
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Jaeb Center for Health Research	Foundation Fighting Blindness

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Characterize Change using Visual Acuity	Best corrected E-ETDRS visual acuity	Baseline and every year until study completion (4 years)
Primary	Characterize Change using Mean Retinal Sensitivity	Measured by fundus-guided microperimetry	Baseline and every year until study completion (4 years)
Primary	Characterize Change in EZ area	Measured by SD-OCT	Baseline and every year until study completion (4 years)
Primary	Characterize Change in Rod- and cone-mediated retinal function	Measured by FST	Baseline and every year until study completion (4 years)
Primary	Characterize Change in Retinal function	Full-field ERG amplitudes and timing in response to rod- and cone-specific stimuli	Baseline and after four years

External Links

•   public website