Clinical trial NCT06323772: Natural History Study in Patients with PDE6A-, PDE6B- and RHO-linked Retinitis Pigmentosa
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Retinitis Pigmentosa
Keywords: Retinal Diseases
Eye Diseases
Eye Diseases, Hereditary
Retinal Dystrophies
Retinal Degeneration
Genetic Diseases, Inborn
Retinitis Pigmentosa
PDE6A, PDE6B, RHO
gene therapy trial
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2024-03-21
Enrollment: 40
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 40 patients with PDE6A, PDE6B, and RHO-based retinitis pigmentosa

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.

Eligibility criteria: 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

Primary outcomes:
measure: Optical coherence tomography (OCT)
timeFrame: 3-5 years
measure: Fundus autofluorescence imaging
timeFrame: 3-5 years
measure: Wide-field fundus photography
timeFrame: 3-5 years
measure: Adaptive optics imaging
timeFrame: 3-5 years
measure: V1 morphology (MRI)
timeFrame: 3-5 years
measure: Diffusion Tensor Imaging (DTI)
timeFrame: 3-5 years
measure: flavoprotein fluorescence (FPF)
timeFrame: 3-5 years
measure: Retinal oxymetry
timeFrame: 3-5 years
measure: Local dark adapted adaptation curves
timeFrame: 3-5 years
measure: best corrected visual acuity (BCVA)
timeFrame: 3-5 years
measure: Static cone perimetry and dark adapted perimetry
timeFrame: 3-5 years
measure: chromatic pupil campimetry (CPC)
timeFrame: 3-5 years
measure: electroretinogram (ERG)
timeFrame: 3-5 years
measure: Virtual reality (VR) functional test
timeFrame: 3-5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Tübingen
country: Germany
facility: Institute for Ophthalmic Research, University Tübingen
state: Baden-Württemberg
Study officials:
affiliation: Department for Opthalmology
name: Katarina Stingl, Prof
role: PRINCIPAL_INVESTIGATOR
References: