Biomarkers in Retinitis Pigmentosa

NCT06306690 | Recruiting DMC

• 1 other identifier: 6401
• Study Type: observational
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to discover biomarkers that demonstrate a correlation between the severity of retinitis pigmentosa (RP) and the thickness of the retinal pigment epithelium (RPE). These biomarkers will serve as prognostic indicators for various kinds of retinitis pigmentosa. The objective of this study is to find biomarkers that establish a correlation between the severity of retinitis pigmentosa and the thickness of the retinal pigment epithelium (RPE), which can serve as a prognostic indicator for Retinitis Pigmentosa.

Conditions

Retinitis Pigmentosa

Keywords

Retinitis Pigmentosa; Retinal degeneration; Multimodal imaging; electroretinography; retinal pigment epithelium and outer retinal atrophy (RORA)

Outcome Measures

Primary Outcomes (1)

• Retinal pigment epithelium changes in Retinitis Pigmentosa.

  Retinal pigment epithelium extent measured with OCT calliper (micrometers).

  14 months

Secondary Outcomes (1)

• Retinitis Pigmentosa biomarkers

  14 months

Study Arms (6)

1. Patients with rhodopsin mutation (RHO)

Following a clinical diagnosis, patients undergo genetic testing. Patients with rhodopsin mutation (RHO) a mutation are categorised into subgroup 1.

Diagnostic Test: OCT, OCT angiography, flicker ERG and Ultra Wide Field retinography and autofluorescence.

2. Patients with pre-mRNA factor 8 (PRPF8) mutation

Following a clinical diagnosis, patients undergo genetic testing. Patients with pre-mRNA factor 8 (PRPF8) mutation are categorised into subgroup 2.

Diagnostic Test: OCT, OCT angiography, flicker ERG and Ultra Wide Field retinography and autofluorescence.

3.Patients a cone-specific phosphodiesterase, i.e. PDE6B, mutation

Following a clinical diagnosis, patients undergo genetic testing. Patients with a cone-specific phosphodiesterase, i.e. PDE6B, mutation are categorised into subgroup 3.

Diagnostic Test: OCT, OCT angiography, flicker ERG and Ultra Wide Field retinography and autofluorescence.

4. Patients with Chromosome 2-Open (C2orf71) mutation

Following a clinical diagnosis, patients undergo genetic testing. Patients with Chromosome 2-Open (C2orf71) mutation are categorised into subgroup 4.

Diagnostic Test: OCT, OCT angiography, flicker ERG and Ultra Wide Field retinography and autofluorescence.

5. Patients with Guanylate Cyclase (GUCY2D) mutation

Following a clinical diagnosis, patients undergo genetic testing. Patients with Guanylate Cyclase (GUCY2D) mutation are categorised into subgroup 5.

Diagnostic Test: OCT, OCT angiography, flicker ERG and Ultra Wide Field retinography and autofluorescence.

6. Patients with RP- specific nuclear receptor (Nr2E3) mutation

Following a clinical diagnosis, patients undergo genetic testing. Patients with RP- specific nuclear receptor (Nr2E3) mutation are categorised into subgroup 6.

Diagnostic Test: OCT, OCT angiography, flicker ERG and Ultra Wide Field retinography and autofluorescence.

Interventions

OCT, OCT angiography, flicker ERG and Ultra Wide Field retinography and autofluorescence. DIAGNOSTIC_TEST

the best visual acuity will be evaluated using decimal tables and then converted to logMar. Ocular fundus examination will be evaluated following pharmacological mydriasis with Tropicamide 1%. OCT will be essential to quantify the central macular thickness and the thickness of the RPE. OCT angiography is a non-invasive method to assess the presence or absence of neovascular membrane and macular flow density. Color and ultra wide field autofluorescence images of the retina will be performed with Zeiss Clarus retinography to search for signs that identify different types of RP and predict their activity and evolution. Electroretinogram flicker (ERG) is a common measure of cone pathway function that is used to study the normal visual system and that of patients with inherited and acquired retinal dysfunction Measurements will be performed using an electrophysiological recording system (CSO). Intermittent stimuli are presented using a Ganzfeld dome (CSO).

1. Patients with rhodopsin mutation (RHO); 2. Patients with pre-mRNA factor 8 (PRPF8) mutation; 3.Patients a cone-specific phosphodiesterase, i.e. PDE6B, mutation; 4. Patients with Chromosome 2-Open (C2orf71) mutation; 5. Patients with Guanylate Cyclase (GUCY2D) mutation; 6. Patients with RP- specific nuclear receptor (Nr2E3) mutation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The patients will be enrolled at the Ophthalmology department of Fondazione Policlinico Universitario A. Gemelli IRCCS. Patients with diverse kinds of RP with genetic confirmation, no other retinal disorders, pressure under 25 mmHg for three months, and no corneal surgery in the past year are included.

You may qualify if:

• Patients who are able to read and sign informed consent
• Patients with Retinitis pigmentosa confirmed by genetic test.
• Patients older than or equal to 18 years of age

You may not qualify if:

• Other retinal diseases such as macular hole, retinal detachment, macular neovascularization.
• Corneal surgery in the last 12 months
• Glaucoma with pressure above 25 mmHg in the last three months.
• Best Correct Visual Acuity below 1/10 in at least one eye.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Maria Cristina Savastano

Roma, 00198, Italy

RECRUITING

Related Publications (11)

• Campochiaro PA, Mir TA. The mechanism of cone cell death in Retinitis Pigmentosa. Prog Retin Eye Res. 2018 Jan;62:24-37. doi: 10.1016/j.preteyeres.2017.08.004. Epub 2017 Sep 27.

  PMID: 28962928 BACKGROUND

• Dias MF, Joo K, Kemp JA, Fialho SL, da Silva Cunha A Jr, Woo SJ, Kwon YJ. Molecular genetics and emerging therapies for retinitis pigmentosa: Basic research and clinical perspectives. Prog Retin Eye Res. 2018 Mar;63:107-131. doi: 10.1016/j.preteyeres.2017.10.004. Epub 2017 Oct 31.

  PMID: 29097191 BACKGROUND

• Cross N, van Steen C, Zegaoui Y, Satherley A, Angelillo L. Retinitis Pigmentosa: Burden of Disease and Current Unmet Needs. Clin Ophthalmol. 2022 Jun 20;16:1993-2010. doi: 10.2147/OPTH.S365486. eCollection 2022.

  PMID: 35757022 BACKGROUND

• Chaumet-Riffaud AE, Chaumet-Riffaud P, Cariou A, Devisme C, Audo I, Sahel JA, Mohand-Said S. Impact of Retinitis Pigmentosa on Quality of Life, Mental Health, and Employment Among Young Adults. Am J Ophthalmol. 2017 May;177:169-174. doi: 10.1016/j.ajo.2017.02.016. Epub 2017 Feb 22.

  PMID: 28237413 BACKGROUND

• Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006 Nov 18;368(9549):1795-809. doi: 10.1016/S0140-6736(06)69740-7.

  PMID: 17113430 BACKGROUND

• Wu KY, Kulbay M, Toameh D, Xu AQ, Kalevar A, Tran SD. Retinitis Pigmentosa: Novel Therapeutic Targets and Drug Development. Pharmaceutics. 2023 Feb 17;15(2):685. doi: 10.3390/pharmaceutics15020685.

  PMID: 36840007 BACKGROUND

• Russell S, Bennett J, Wellman JA, Chung DC, Yu ZF, Tillman A, Wittes J, Pappas J, Elci O, McCague S, Cross D, Marshall KA, Walshire J, Kehoe TL, Reichert H, Davis M, Raffini L, George LA, Hudson FP, Dingfield L, Zhu X, Haller JA, Sohn EH, Mahajan VB, Pfeifer W, Weckmann M, Johnson C, Gewaily D, Drack A, Stone E, Wachtel K, Simonelli F, Leroy BP, Wright JF, High KA, Maguire AM. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017 Aug 26;390(10097):849-860. doi: 10.1016/S0140-6736(17)31868-8. Epub 2017 Jul 14.

  PMID: 28712537 BACKGROUND

• Iftikhar M, Lemus M, Usmani B, Campochiaro PA, Sahel JA, Scholl HPN, Shah SMA. Classification of disease severity in retinitis pigmentosa. Br J Ophthalmol. 2019 Nov;103(11):1595-1599. doi: 10.1136/bjophthalmol-2018-313669. Epub 2019 Jan 31.

  PMID: 30705041 BACKGROUND

• Savastano MC, Falsini B, Ferrara S, Scampoli A, Piccardi M, Savastano A, Rizzo S. Subretinal Pigment Epithelium Illumination Combined With Focal Electroretinogram and Visual Acuity for Early Diagnosis and Prognosis of Non-Exudative Age-Related Macular Degeneration: New Insights for Personalized Medicine. Transl Vis Sci Technol. 2022 Jan 3;11(1):35. doi: 10.1167/tvst.11.1.35.

  PMID: 35077530 BACKGROUND

• Guymer RH, Rosenfeld PJ, Curcio CA, Holz FG, Staurenghi G, Freund KB, Schmitz-Valckenberg S, Sparrow J, Spaide RF, Tufail A, Chakravarthy U, Jaffe GJ, Csaky K, Sarraf D, Mones JM, Tadayoni R, Grunwald J, Bottoni F, Liakopoulos S, Pauleikhoff D, Pagliarini S, Chew EY, Viola F, Fleckenstein M, Blodi BA, Lim TH, Chong V, Lutty J, Bird AC, Sadda SR. Incomplete Retinal Pigment Epithelial and Outer Retinal Atrophy in Age-Related Macular Degeneration: Classification of Atrophy Meeting Report 4. Ophthalmology. 2020 Mar;127(3):394-409. doi: 10.1016/j.ophtha.2019.09.035. Epub 2019 Sep 30.

  PMID: 31708275 BACKGROUND

• Placidi G, Maltese PE, Savastano MC, D'Agostino E, Cestrone V, Bertelli M, Chiurazzi P, Maceroni M, Minnella AM, Ziccardi L, Parisi V, Rizzo S, Falsini B. Retinitis Pigmentosa Associated with EYS Gene Mutations: Disease Severity Staging and Central Retina Atrophy. Diagnostics (Basel). 2023 Feb 23;13(5):850. doi: 10.3390/diagnostics13050850.

  PMID: 36899994 BACKGROUND

MeSH Terms

Conditions

Retinitis Pigmentosa; Retinal Degeneration

Interventions

Tomography, Optical Coherence

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Dystrophies; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Tomography, Optical; Optical Imaging; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Investigative Techniques

Central Study Contacts

Stanislao Rizzo, MD, Prof

CONTACT

0630151; stanislao.rizzo@policlinicogemelli.it

Valentina Cestrone

CONTACT

3200609905; valentina.cestrone@guest.policlinicogemelli.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 10, 2024
• First Posted: March 12, 2024
• Study Start: February 1, 2024
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: March 12, 2024

Record last verified: 2024-03

Locations

IT (1)