Clinical and Genetic Testing of Patients With Usher Syndrome

Prospective Open Label Clinical and Genetic Testing of Patients With Usher Syndrome

This study is aimed to characterize Russian population of Usher patients.

Study Overview

• Status: Completed
• Conditions: Retinitis Pigmentosa; Usher Syndrome; Congenital Deafness

Detailed Description

This study is aimed to characterize Russian population of Usher patients.

Tasks:

Stage 1. Formation of the primary cohort of patients. Patients pre-recruiting will be performed based on Deaf-Blind Support Foundation "Con-nection" patient database analysis. Patients with clinically confirmed Usher syndrome will be evaluated according to available data of the clinical examination.

Stage 2. Clinical examination of patients.

Each patient will undergo the following diagnostic procedures according to the unified protocol:

• Visometry (with correction and without correction)
• Ophthalmoscopy
• Perimetry
• Optical coherence tomography
• Electroretinography
• Visually evoked potentials
• Refractometry
• Pneumotonometry
• Biomicroscopy
• Tonal audiometry
• Electronic audiometry (ASSR test)
• Acoustic impedance measurement
• Vestibulometry
• Electronystagmography
• Any additional examinations and consultations if necessary

Medical record will be developed and maintained for each patient consisting results of extended clinical examination.

Stage 3. Genetic study of patients. All enrolled patients will undergo single 4 ml peripheral venous blood sampling. DNA will be extracted from leucocytes. DNA samples will be analyzed and placed for long-term storage in liquid nitrogen. Statistical and bioinformatic analysis of detected genetic mutations in the study cohort will be performed.

• Study Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • Federal State Budgetary Institution "Research Center for Medical Genetics"
  • Moscow, Russian Federation, 117593
    • Deaf-Blind Support Foundation "Con-nection"
  • Moscow, Russian Federation, 123098
    • State Research Center Burnasyan Federal Medical Biophysical Center Federal Medical-Biological Agency
  • Moscow, Russian Federation, 123182
    • Scientific and Clinical Center for Otorhinolaryngology of FMBA of Russia
  • Moscow, Russian Federation, 125167
    • Oftalmic LLC
  • Moscow, Russian Federation, 129085
    • Autonomous nonprofit organization "Scientific and industrial laboratory "Sensor technology for deafblind"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

It is assumed that at least 28 patients of the Russian population of men and women aged 18 to 65 years, with verified diagnosis of Usher syndrome (type I, II or III as defined by the Usher syndrome consortium), will take part in this research study.

Description

Inclusion Criteria:

• Patient fulfill the clinical characteristics for Usher syndrome type I, II or III as defined by the Usher syndrome consortium
• According to the results of audiometry, hearing loss is moderate or severe (level of acoustic threshold of audibility is 41 decibel and higher).
• Results of perimetry for each eye show narrowing for 15 degrees or more.
• Patient is familiar with Participant information sheet
• Patient signed informed consent form

Non-inclusion Criteria:

• Participation in other clinical trials (or administration of investigational drugs) during 3 months prior inclusion
• Any conditions limiting compliance (dementia, neuropsychiatric disease, drug and alcohol abuse etc.)
• Medical history of traumatic injury of eyes, barotrauma, concussion, craniocerebral trauma, cerebrovascular accident

Exclusion Criteria:

• Patient's refusal from the further participation in the trial
• Decompensated diabetes mellitus
• Severe coronary artery disease
• Chronic infectious disease
• Patients with malignant tumors including postoperative period, patients receiving chemotherapy and/or radiotherapy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in structures of fundus of the eye-1	Measured by ophthalmoscopy	Up to 4 weeks
Changes in visual field	Measured by perimetry	Up to 4 weeks
Changes in brain visual cortex neural pathways	Measured by visually evoked potentials	Up to 4 weeks
Changes in optical refraction	Measured by refractometry	Up to 4 weeks
Changes in intraocular pressure	Measured by pneumotonometry	Up to 4 weeks
Changes in the lens, cornea, anterior segment of the eye	Measured by biomicroscopy	Up to 4 weeks
Changes in visual acuity	Measured by visometry	Up to 4 weeks
Changes in structures of fundus of the eye-2	Measured by optical coherence tomography	Up to 4 weeks
Changes in retinal ganglion cell dysfunction	Measured by electroretinography	Up to 4 weeks
Changes in hearing-1	Measured by tonal audiometry	Up to 4 weeks
Changes in hearing-2	Measured by electronic audiometry (ASSR test)	Up to 4 weeks
Changes in efficient sound transmission in the middle ear	Measured by acoustic impedance measurement	Up to 4 weeks
Changes in vestibular functions	Measured by vestibulometry	Up to 4 weeks
Changes in vestibular reactions	Measured by electronystagmography	Up to 4 weeks

Collaborators and Investigators

• Sponsor: Sensor Technology for Deafblind
• Collaborators: Deaf-Blind Support Foundation Con-nection; Federal State Budgetary Institution Research Center for Medical Genetics; Oftalmic LLC; Burnasyan Federal Medical Biophysical Center; Scientific and Clinical Center for Otorhinolaryngology of FMBA of Russia; ANO Laboratory Sensor-Tech
• Investigators: Principal Investigator: Vladimir N Trubilin, MD, PhD, Prof, State Research Center Burnasyan Federal Medical Biophysical Center Federal Medical-Biological Agency

Publications and helpful links

General Publications

• Ivanova ME, Trubilin VN, Atarshchikov DS, Demchinsky AM, Strelnikov VV, Tanas AS, Orlova OM, Machalov AS, Overchenko KV, Markova TV, Golenkova DM, Anoshkin KI, Volodin IV, Zaletaev DV, Pulin AA, Nadelyaeva II, Kalinkin AI, Barh D. Genetic screening of Russian Usher syndrome patients toward selection for gene therapy. Ophthalmic Genet. 2018 Dec;39(6):706-713. doi: 10.1080/13816810.2018.1532527. Epub 2018 Oct 25.

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2017
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: October 2, 2017
• First Submitted That Met QC Criteria: October 23, 2017
• First Posted (Actual): October 24, 2017

Study Record Updates

• Last Update Posted (Actual): April 3, 2019
• Last Update Submitted That Met QC Criteria: April 1, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Disease; Congenital Abnormalities; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Otorhinolaryngologic Diseases; Ear Diseases; Eye Diseases, Hereditary; Retinal Dystrophies; Sensation Disorders; Abnormalities, Multiple; Hearing Disorders; Vision Disorders; Deaf-Blind Disorders; Hearing Loss, Sensorineural; Blindness; Hearing Loss; Syndrome; Retinitis; Retinitis Pigmentosa; Deafness; Usher Syndromes
• Other Study ID Numbers: RU-USH-09-2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No