Natural History Study in Patients With PDE6A-, PDE6B- and RHO-linked Retinitis Pigmentosa

Exploration of New Sensitive Clinical Readouts and Biomarkers That Can be Used as Clinical Endpoints Tailored to Monitor Treatment Effects in PDE6A-, PDE6B- and RHO-linked Retinitis Pigmentosa: a Non-interventional Trial

The aim of the study is to apply a novel clinical investigation protocol in patients with Phosphodiesterase 6A (PDE6A), PDE6B and Rhodopsin (RHO)-based retinitis pigmentosa. This novel, multimodal clinical examination protocol describes and correlates structural, functional and metabolic aspects during natural disease development.

Test-retest variability of new measurements as well as correlations of the structural, functional, and metabolic changes will be defined to be able to define well-suited readouts for safety and efficacy of future treatment developments before they reach the clinical phase.

Study Overview

• Status: Active, not recruiting
• Conditions: Retinitis Pigmentosa

Detailed Description

Hereditary retinal diseases such as retinitis pigmentosa are rare genetic diagnoses of the retina with chronic lifelong progression, often leading to blindness. Progression varies greatly between individuals. PDE6A, PDE6B and RHO related retinitis pigmentosa phenotypes are typical retinal dystrophies with early onset of rod dysfunctions and a rather slow progression of the cone dysfunction with progression to complete blindness in later adulthood.

Classical gene therapy could improve the function of the rods if successful, although the changes may only be very small and need to be measured using sensitive methods. In contrast, neuroprotective therapeutic approaches could slow down these slow processes even further, which would be extremely difficult to prove as clinical efficacy in a future clinical trial with very individual courses.

In order to have clinical examination methods in the future that can prove the safety and efficacy of neuroprotective approaches, very sensitive examination methods are needed whose test variability is also known. In addition, a neuroprotective treatment method can positively influence the metabolic state of the retina, which, in contrast to slowing down a slow degeneration process, would be a demonstrable effect if the metabolism of the retina can be examined in a clinically relevant way.

For these reasons, the investigators will focus on the above-mentioned genotypes of retinitis pigmentosa in a non-interventional study in order to collect and correlate structural, functional and metabolic examinations of the retina.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

Study Locations

• Germany
  • Baden-Wurttemberg
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Institute for Ophthalmic Research, University Tübingen

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

40 patients with PDE6A, PDE6B, and RHO-based retinitis pigmentosa

Description

Inclusion Criteria:

• Age: from 5 years of age
• Patient with PDE6A, PDE6B, and RHO-based retinitis pigmentosa
• Patient and/or legal representatives are willing and able to give written informed consent

Exclusion Criteria:

• severe general disease, that would make longer examinations not possible

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
PDE6A patients; 15 patients with mutation in PDE6A
PDE6B patients; 15 patients with mutation in PDE6B
RHO patients; 10 patients with mutation in RHO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optical coherence tomography (OCT)	OCT volume scans of the macular region, morphological examination	3-5 years
Fundus autofluorescence imaging	Fundus autofluorescence imaging, morphological examination	3-5 years
Wide-field fundus photography	Wide-field fundus photography, morphological examination	3-5 years
Adaptive optics imaging	Adaptive optics imaging, morphological examination	3-5 years
V1 morphology (MRI)	MRI, morphological examination	3-5 years
Diffusion Tensor Imaging (DTI)	DTI of the optical pathway , morphological examination	3-5 years
flavoprotein fluorescence (FPF)	FPF, metabolic readout	3-5 years
Retinal oxymetry	Retinal oxymetry, metabolic readout , Local dark adapted adaptation curves	3-5 years
Local dark adapted adaptation curves	Local dark adapted adaptation curves , metabolic readout ,	3-5 years
best corrected visual acuity (BCVA)	BCVA, functional diagnostics	3-5 years
Static cone perimetry and dark adapted perimetry	Static cone perimetry and dark adapted perimetry , functional diagnostics	3-5 years
chromatic pupil campimetry (CPC)	scotopic and photopic CPC , functional diagnostics	3-5 years
electroretinogram (ERG)	Functional ERG (new flickers 9, 15, 31 Hertz) , functional diagnostics	3-5 years
Virtual reality (VR) functional test	VR functional test, functional diagnostics	3-5 years

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Investigators: Principal Investigator: Katarina Stingl, Prof, Department for Opthalmology

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: March 7, 2024
• First Submitted That Met QC Criteria: March 14, 2024
• First Posted (Actual): March 21, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Eye Diseases; Genetic Diseases, Inborn; Retinitis Pigmentosa; Eye Diseases, Hereditary; Retinal Diseases; Retinal Degeneration; gene therapy trial; Retinal Dystrophies; PDE6A, PDE6B, RHO
• Additional Relevant MeSH Terms: Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Retinal Diseases; Genetic Diseases, Inborn; Eye Diseases; Retinitis Pigmentosa; Retinal Degeneration; Retinal Dystrophies; Eye Diseases, Hereditary; Night Blindness, Congenital Stationary, Autosomal Dominant 1; Night Blindness, Congenital Stationary, Autosomal Dominant 2
• Other Study ID Numbers: RDC-RP-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No