CNGB1 and Allied Disorders

Study of CNGB1 Retinitis Pigmentosa and Allied Hereditary Disorders

Mutations in the rod-expressed gene, cyclic nucleotide-gated channel beta subunit (CNGB1) and associated inborn errors in metabolism are causes of retinal disease that causes progressive loss of vision. Retinitis pigmentosa (RP) is a major cause of untreatable blindness associated with CNGB1 (CNGB1-RP). RP involves the death of photoreceptor cells that can be caused by mutations in a number of different genes. Treatment by gene therapy could prevent blindness in cases of inherited retinal dystrophies including RP. In the future RP due to mutations in CNGB1 may be treatable by gene therapy since this form of photoreceptor degeneration involves a slow loss of rod photoreceptor cells. This provides a wide window of opportunity for the identification of patients and initiation of treatment. Our efforts are directed toward developing gene therapy as a treatment. To this end, our objective is to better understand the disease process of CNGB1-RP and other allied inherited disorders so that we can develop clinical tests to measure the outcomes of treatment.

Study Overview

• Status: Recruiting
• Conditions: Retinitis Pigmentosa Associated With CNGB1 Mutations
• Intervention / Treatment: Other: No intervention, this is a natural history progression study

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Recruiting
    • Institut de la Vision/Centre de maladies rares du Centre Hospitalier National Ophtalmologique des Quinze-Vingts
    • Contact: Isabelle Audo, MD, PhD; Phone Number: +33 1 40 02 14 30; Email: isabelle.audo@inserm.fr
    • Contact: Camille Andrieu, MD; Phone Number: +33 1 40 02 14 51; Email: candrieu@15-20.fr
    • Principal Investigator: Isabelle Audo, MD, PhD
• Germany
  • Tuebingen, Germany
    • Recruiting
    • Eberhard Karls University Tubingen
    • Contact: Laura Kuehlewein, MD; Phone Number: +49 07071 29-88088; Email: laura.kuehlewein@med.uni-tuebingen.de
    • Contact: Katarina Stingl, MD; Phone Number: +49 7071 29 87421; Email: katarina.stingl@med.uni-tuebingen.de
    • Principal Investigator: Eberhart Zrenner, MD
  • Bavaria
    • München, Bavaria, Germany, 80336
      • Recruiting
      • Klinikum der Universität München University Eye Hospital, Ludwig-Maximilians-University (LMU) Munich
      • Contact: Claudia Priglinger, PD Dr.; Phone Number: +49 (0)89 4400 53717; Email: claudia.priglinger@med.uni-muenchen.de
      • Principal Investigator: Maximilian Gerhardt, MD
      • Contact: Stefan May; Phone Number: +49 (0)89 4400-53146; Email: Stefan.May@med.uni-muenchen.de
      • Principal Investigator: Stylianos Michalakis, PhD
• United Kingdom
  • London, United Kingdom
    • Not yet recruiting
    • Moorfields Eye Hospital NHS Foundation Trust
    • Contact: Simona D Esposti, MD; Phone Number: (+44) 207 566 2263; Email: s.esposti@nhs.net
    • Contact: Omar Mahroo, PhD; Phone Number: (+44) 207 566 2263; Email: o.mahroo@ucl.ac.uk
    • Principal Investigator: Simona D Esposti, MD
• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Dr. Stephen H. Tsang
      • Contact: Stephen H Tsang, MD, PhD; Phone Number: 212-342-1186; Email: sht2@columbia.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Wills Eye Hospital
      • Contact: Rebecca Procopio, CGC; Phone Number: 267-733-9681; Email: rprocopio@willseye.org
      • Contact: Tobin BT Thuma, DO; Phone Number: 215-928-3240; Email: tthuma@willseye.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients are expected to present to the clinic at all age groups; enrollment of subjects <18 years of age will be obtained by informed consent in the company of a parent or legal guardian. There will also be no gender-or ethnic/racial specific inclusion criteria. The enrollment of non-English speaking subjects is not expected.

Description

Inclusion Criteria:

• Diagnosis of CNGB1-associated RP by study physician, who are trained retinal specialists in the university clinic
• Must be able to commit to 4 follow-up study visits (3 years)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
We will be looking to identify what the best outcome measurements will be for CNGB1-RP in order to use these measurements in a future clinical trial.	Both structural imaging and functional tests will be used to characterize the natural history progression of CNGB1-RP.	2 days, 1 time per year, for 3 years
Medmont Dark Adapted Chromatic (DAC) Automated Perimeter		1 time per year, for 3 years
Full-field ERG (ISCEV Protocol)		1 time per year, for 3 years
Optical Coherence Tomography (OCT)		1 time per year, for 3 years
Fundus Autofluorescence (FAF)		1 time per year, for 3 years
Near-infrared fundus autofluorescence (NIR-AF)		1 time per year, for 3 years
Quantitative Fundus Autofluorescence (qAF)		1 time per year, for 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best-corrected Visual Acuity (BCVA)		1 time per year, for 3 years
Complete Ophthalmic Exam		2 time per year, for 3 years
Color Fundus Photos		1 time per year, for 3 years
MAIA Microperimetry	if available	1 time per year, for 3 years
NIDEK Microperimetry	if available	1 time per year, for 3 years
Goldman Kinetic Visual Field		1 time per year, for 3 years
Light-adapted Static Perimetry		1 time per year, for 3 years
Panel D-15 Colour Vision (desat.)		1 time per year, for 3 years
Dark-adapted Chromatic Perimetry		1 time per year, for 3 years
Full-field Stimulus Testing (FST)	Optional	1 time per year, for 3 years

Other Outcome Measures

Outcome Measure	Time Frame
Demographics/medical history	1 time only at baseline
Concomitant medications/adverse events	1 time only at baseline

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Ludwig-Maximilians - University of Munich; Moorfields Eye Hospital NHS Foundation Trust; Wills Eye; Michigan State University; Universität Tübingen; La Fondation Voir et Entendre

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2019
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: August 7, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (Actual): November 20, 2020

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Retinitis Pigmentosa; CNGB1; Natural Progression
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Retinal Dystrophies; Retinitis; Retinitis Pigmentosa
• Other Study ID Numbers: AAAS1160

Drug and device information, study documents

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