Rate of Progression in USH2A-related Retinal Degeneration
Açar sözlər
Mücərrəd
Təsvir
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
Tarixlər
| Son Doğrulandı: | 01/31/2020 |
| İlk təqdim: | 05/03/2017 |
| Təxmini qeydiyyat təqdim edildi: | 05/04/2017 |
| İlk Göndərmə: | 05/08/2017 |
| Son Yeniləmə Göndərildi: | 02/06/2020 |
| Son Yeniləmə Göndərildi: | 02/10/2020 |
| Həqiqi Təhsilin Başlama Tarixi: | 08/10/2017 |
| Təxmini İlkin Tamamlanma Tarixi: | 12/31/2022 |
| Təxmini İşin Tamamlanma Tarixi: | 12/31/2022 |
Vəziyyət və ya xəstəlik
Faza
Qol Qrupları
| Qol | Müdaxilə / müalicə |
|---|---|
| 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 |
Uyğunluq Kriteriyaları
| Təhsil üçün uyğun yaşlar | 8 Years Üçün 8 Years |
| Təhsilə Uyğun Cinslər | All |
| Nümunə götürmə metodu | Probability Sample |
| Sağlam Könüllüləri qəbul edir | Bəli |
| Kriteriyalar | 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) |
Nəticə
İlkin nəticə tədbirləri
1. Change in Visual Field Sensitivity [Baseline and every year until study completion (4 years)]
2. Change in Visual Acuity [Baseline and every year until study completion (4 years)]
3. Change in Mean Retinal Sensitivity [Baseline and every year until study completion (4 years)]
4. Change in EZ area [Baseline and every year until study completion (4 years)]
5. Change in Rod- and cone-mediated retinal function [Baseline and every year until study completion (4 years)]
6. Change in Retinal function [Baseline and after four years]
