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Rate of Progression in USH2A Related Retinal Degeneration (RUSH2A)

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ClinicalTrials.gov Identifier: NCT03146078
Recruitment Status : Active, not recruiting
First Posted : May 9, 2017
Last Update Posted : July 4, 2019
Sponsor:
Collaborators:
Foundation Fighting Blindness
Duke University
Oregon Health and Science University
Information provided by (Responsible Party):
Jaeb Center for Health Research

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).

Condition or disease
Usher Syndrome, Type 2A Retinitis Pigmentosa 39

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:

  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

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Study Type : Observational
Actual Enrollment : 127 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Rate of Progression in USH2A Related Retinal Degeneration
Actual Study Start Date : August 11, 2017
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2023


Group/Cohort
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



Primary Outcome Measures :
  1. Change in Visual Field Sensitivity [ Time Frame: Baseline and every year until study completion (4 years) ]
    Measured by static perimetry with topographic analysis (Hill of Vision)

  2. Change in Visual Acuity [ Time Frame: Baseline and every year until study completion (4 years) ]
    Best corrected E-ETDRS visual acuity

  3. Change in Mean Retinal Sensitivity [ Time Frame: Baseline and every year until study completion (4 years) ]
    Measured by fundus-guided microperimetry

  4. Change in EZ area [ Time Frame: Baseline and every year until study completion (4 years) ]
    Measured by SD-OCT

  5. Change in Rod- and cone-mediated retinal function [ Time Frame: Baseline and every year until study completion (4 years) ]
    Measured by FST

  6. 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


Biospecimen Retention:   Samples With DNA
Saliva samples


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   8 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   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
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03146078


Locations
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United States, California
University of California, San Francisco
San Francisco, California, United States, 94143-0344
United States, Florida
Vitreo-Retinal Associates
Gainesville, Florida, United States, 32607
United States, Maryland
Wilmer Eye Institute at Johns Hopkins
Baltimore, Maryland, United States, 21287-9277
United States, Massachusetts
Massachusetts Eye and Ear
Boston, Massachusetts, United States, 02114
United States, Michigan
Kellogg Eye Center, University of Michigan
Ann Arbor, Michigan, United States, 48105
United States, North Carolina
Duke University Eye Center
Durham, North Carolina, United States, 27710
United States, Oregon
OSHU Casey Eye Institute
Portland, Oregon, United States, 97239
United States, Texas
Retina Foundation of the Southwest
Dallas, Texas, United States, 75231
Baylor Eye Physicians and Surgeons
Houston, Texas, United States, 77030
United States, Utah
Moran Eye Center, University of Utah
Salt Lake City, Utah, United States, 84107
United States, Wisconsin
Medical College of Wiconsin
Milwaukee, Wisconsin, United States, 53226
Canada
Hospital for Sick Children
Toronto, Canada
France
Institut de la Vision
Paris, France, 75012
Germany
University of Tubingen
Tübingen, Germany
Netherlands
Radboud University
Nijmegen, Netherlands
United Kingdom
Moorfields Eye Hostpital
London, United Kingdom
Sponsors and Collaborators
Jaeb Center for Health Research
Foundation Fighting Blindness
Duke University
Oregon Health and Science University
Investigators
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Study Chair: Jacque Duncan, MD University of California, San Francisco
  Study Documents (Full-Text)

Documents provided by Jaeb Center for Health Research:
Study Protocol  [PDF] October 5, 2018


Additional Information:
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Responsible Party: Jaeb Center for Health Research
ClinicalTrials.gov Identifier: NCT03146078     History of Changes
Other Study ID Numbers: RUSH2A
First Posted: May 9, 2017    Key Record Dates
Last Update Posted: July 4, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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 primary manuscript.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Deafness
Hearing Loss
Hearing Loss, Sensorineural
Retinitis
Retinitis Pigmentosa
Retinal Degeneration
Usher Syndromes
Retinal Diseases
Eye Diseases
Eye Diseases, Hereditary
Retinal Dystrophies
Genetic Diseases, Inborn
Deaf-Blind Disorders
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Blindness
Vision Disorders
Abnormalities, Multiple
Congenital Abnormalities
Signs and Symptoms