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

Retinitis Pigmentosa Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06323772
• Other study ID #: RDC-RP-01
• Status: Recruiting
• Start date: November 17, 2023
• Est. completion date: March 2027

Study information

• Verified date: February 2024
• Source: University Hospital Tuebingen
• Contact: Katarina Stingl, Prof
• Phone: 070712988088
• Email: katarina.stingl[@]med.uni-tuebingen.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: March 2027
• Est. primary completion date: March 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Retinitis
• Retinitis Pigmentosa

Locations

Country	Name	City	State
Germany	Institute for Ophthalmic Research, University Tübingen	Tübingen	Baden-Württemberg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Tuebingen

Country where clinical trial is conducted

Germany, 

Outcome

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