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

Recruiting

• Conditions: Retinitis Pigmentosa

• Registration Number: NCT06323772
• Lead Sponsor: University Hospital Tuebingen

Brief Summary

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.

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 Timeline

• Study Start: 2023-11-17
• Study First Submitted: 2024-03-07
• Study First Submitted QC: 2024-03-14
• Study First Posted: 2024-03-21
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-30
• Primary Completion: 2027-03
• Study Completion: 2027-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Trial Locations

Locations (1)

Institute for Ophthalmic Research, University Tübingen; 🇩🇪 Tübingen, Baden-Württemberg, Germany