NCT04820244: CRUSH

Characterizing Rate of Progression in USHer Syndrome (CRUSH) Study

Status unknown Last updated 29 April 2022

What this trial tests

trial testing No intervention in Usher Syndrome, Type 2A in 36 participants. Status unknown.

Timeline

11 February 2019

Primary endpoint
2 March 2024

2 March 2024

Quick facts

Lead sponsor	Radboud University Medical Center
Status	Status unknown
Study type	OBSERVATIONAL
Enrollment	36
Start date	11 February 2019
Primary completion	2 March 2024
Estimated completion	2 March 2024
Sites	1 location across Netherlands

Drugs / interventions tested

• No intervention

Conditions studied

• Usher Syndrome, Type 2A — all drugs for Usher Syndrome, Type 2A →
• Retinitis Pigmentosa — all drugs for Retinitis Pigmentosa →
• USH2A — all drugs for USH2A →

Sponsor

Radboud University Medical Center

Who can join

Adults 16 to 55, any sex, with Usher Syndrome, Type 2A or Retinitis Pigmentosa. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Mutations in USH2A give rise to two phenotypes: Usher syndrome type 2a (USH2A) and nonsyndromic RP (USH2A associated nsRP). Usher syndrome is the most common form of congenital deafblindness. Patients with Usher syndrome are hearing impaired or profoundly deaf from birth and this can be rehabilitated with hearing aids or a cochlear implant. Furthermore, these patients develop retinitis pigmentosa (RP), a slowly progressive type of retinal degeneration that usually starts in the first or second decade of life. In both USH2A and nsRP patients the disease leads to severe visual impairment and eventually blindness around the 50th-70th year of life. There are no treatment options for the retinal degeneration. We do not know if they also suffer from balance complaints.

Currently, genetic therapy for Usher syndrome type 2 and USH2A associated nsRP is in development. But to measure the effect of a (genetic) therapy, it is crucial to know the detailed natural course of the visual and hearing deterioration over time. Several genetic therapy studies for other disorders are currently delayed, because the natural history of the disease has not been studied in detail previously.

The main objective is to map the natural course of the visual and hearing deterioration in Usher Syndrome 2 and USH2A associated nsRP for upcoming genetic therapy studies. Secondary objectives are: 1) To determine the necessary type of (combined) examinations, the sample size and length of studies (in years) essential to evaluate future genetic therapy in Usher syndrome. 2) To improve counselling of patients with Usher syndrome type 2 and USH2A associated nsRP with detailed information on the prognosis. 3) To identify additional etiological factors that explain variability in hearing impairment by adding questionnaires and psychophysical audiometric tests; and to assess the vestibular phenotype in Usher syndrome type 2 and USH2A associated nsRP patients.

This is a longitudinal, prospective natural history study. The study population consists of healthy human volunteers, 16 - 55 yr old with a confirmed genetic diagnosis of Usher Syndrome type 2 or and USH2A associated nsRP.

The main study endpoint is the natural course of the visual and hearing deterioration in Usher Syndrome type 2 and USH2A associated nsRP, over a time span of 4 years.

There are no risks associated with participation.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Genetic Characteristics and Variation Spectrum of USH2A-Related Retinitis Pigmentosa and Usher Syndrome.
   Li W, Jiang XS, Han DM, Gao JY, et al · · 2022 · cited 13× · PMID 36110214 · DOI 10.3389/fgene.2022.900548
2. Evaluation of Sleep Quality and Fatigue in Patients with Usher Syndrome Type 2a.
   Hendricks JM, Metz JR, Velde HM, Weeda J, et al · · 2023 · cited 3× · PMID 37334034 · DOI 10.1016/j.xops.2023.100323
3. Actigraphy-based assessment of circadian rhythmicity and sleep in patients with Usher syndrome type 2a: A case-control study.
   Hendricks JM, Metz JR, Boss HM, Collin RWJ, et al · · 2025 · cited 2× · PMID 39740053 · DOI 10.1111/jsr.14456