Validation of Human Drugs Target of Repurposed Drugs and Novel Therapies

The cross-sectional observational clinical study related to rare eye diseases is a multi-center study in which the hypothesis is that neurokinin 1 receptor and/or substance P expression is increased in REDs associated with inflammation/pain. Moreover, the following alternative targets are: VEGF, PAX6 and pro-inflammatory cytokine.

The following procedures are performed specifically for the study: samples of blood, tear fluid and impression cytology.

Precisely during the ophthalmological exam performed according to normal clinical practice (uncorrected visual acuity, best spectacle corrected visual acuity, corneal topography, corneal pachymetry and the slit lamp pictures) investigator's team collect the samples of blood, tear fluid and impression cytology to evaluate the goal of the study.

Study Overview

• Status: Not yet recruiting
• Conditions: Rare Diseases; Corneal Neovascularization; Limbal Stem Cell Deficiency; Aniridia; Neurotrophic Keratopathy; Ocular Cicatricial Pemphigoid; Ocular Graft-versus-host Disease; EEC Syndrome

• Study Type: Observational
• Enrollment (Estimated): 274

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of 137 patients, each of them will present with one of the 7 diseases under study (REDs).

The control group will consist of 137 patients not presenting the previous reported REDs.

Description

Inclusion Criteria:

Inclusion Criteria for study group

• Women and men with age equal or higher than 18 years (patients in reproductive age may be included in the study).
• Willingness and ability to read and understand the informed consent.
• Diagnosis (including genotype, if needed) of REDs.

Inclusion Criteria for control group

• Women and men with age equal or higher than 18 years (patients in reproductive age may be included in the study).
• Willingness and ability to read and understand the informed consent.
• Non - diagnosis of REDs.

Exclusion Criteria:

Exclusion Criteria for study group

Patients who meet these criteria will be excluded from participation in the study:

• Pregnancy, breastfeeding.
• Active ocular infection.
• Descemetocele/impending corneal perforation.
• Recent (less than 3 months) ocular surgery.
• Recent (less than 1 month) change in topical medications type and frequency.

Exclusion Criteria for control group

Patients who meet these criteria will be excluded from participation in the study:

• Pregnancy, breastfeeding.
• Active ocular infection.
• Descemetocele/impending corneal perforation.
• Recent (less than 3 months) ocular surgery.
• Recent (less than 1 month) change in topical medications type and frequency.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Control group
Patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To quantify the expression of molecular/cellular/genomic targets in the REDs and control group to detect statistically significant and clinically relevant differences.	Evaluation of NK1R transcription levels in PBMC, substance P and VEGF protein levels in the tear fluid, pro-inflammatory cytokines transcription levels in conjunctival tissue. NK1R and pro-inflammatory cytokines are expressed as fold change compared to control group. Substance P and VEGF are expressed as ng/ml.	Day 0 (enrollment day).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To correlate the expression of molecular/cellular genomic targets with the clinical phenotype/quality of life/pain symptoms in patients with the 7 rare diseases and in the control group so as to detect possible risk factors.	Levels of NK1R, substance P, VEGF, and pro-inflammatory cytokines correlated with pictures, questionnaires, uncorrected visual acuity, best spectacle corrected visual acuity, corneal topography, corneal pachymetry and the slit lamp pictures acquired during the ophthalmologic exam.	Day 0 (enrollment day).

Collaborators and Investigators

• Sponsor: IRCCS Ospedale San Raffaele

Publications and helpful links

Helpful Links

• European Commission, ERN-EYE: a European Reference Network dedicated to Rare Eye Diseases. Accessed 29 December 2021
• European Blind Union, About Blindness and Partial Sight: Facts and Figures. Accessed 26 August 2022
• Restore Vision site

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: April 30, 2024
• First Submitted That Met QC Criteria: May 8, 2024
• First Posted (Actual): May 14, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: VEGF; Cytokine; Blood; Substance P; Aniridia; Corneal Neovascularization; Limbal Stem Cell Deficiency; PBMC; Impression cytology; Tear; Neurotrophic Keratopathy; Rare Eye Diseases; Ocular Graft-versus-host Disease; Ocular Cicatricial Pemphigoid; Molecular targets; Cellular targets; Genomic targets; NK1R
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease Attributes; Congenital Abnormalities; Eye Abnormalities; Genetic Diseases, Inborn; Uveal Diseases; Eye Diseases, Hereditary; Skin Diseases, Vesiculobullous; Conjunctival Diseases; Corneal Diseases; Metaplasia; Iris Diseases; Neovascularization, Pathologic; Pemphigoid, Bullous; Graft vs Host Disease; Corneal Neovascularization; Rare Diseases; Aniridia; Pemphigoid, Benign Mucous Membrane; Limbal Stem Cell Deficiency
• Other Study ID Numbers: RV-WP2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No