## Protocol Section
### Identification Module
**NCT ID:** NCT06412718

**Brief Title:** Validation of Human Drugs Target of Repurposed Drugs and Novel Therapies

**Official Title:** Validation of Human Drugs Target of Repurposed Drugs and Novel Therapies

#### Organization Study ID Info
**ID:** RV-WP2
#### Organization
**Class:** OTHER
**Full Name:** IRCCS Ospedale San Raffaele
### Status Module
#### Completion Date
**Date:** 2026-04

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-14

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-08

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-04

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05

**Type:** ESTIMATED

**Status Verified Date:** 2024-04

#### Study First Post Date
**Date:** 2024-05-14
**Type:** ACTUAL
**Study First Submit Date:** 2024-04-30
**Study First Submit QC Date:** 2024-05-08
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** IRCCS Ospedale San Raffaele

#### Responsible Party

**Investigator Affiliation:** IRCCS Ospedale San Raffaele

**Investigator Full Name:** Giulio Ferrari

**Investigator Title:** Professor of Ophthalmology-San Raffaele Vita Salute University, Cornea and Ocular Surface Unit; Head-Eye Repair Lab San Raffaele Scientific Institute

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** 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.

### Conditions Module

**Conditions:**

- Rare Diseases

- Aniridia

- Neurotrophic Keratopathy

- Limbal Stem Cell Deficiency

- Ocular Graft-versus-host Disease

- Ocular Cicatricial Pemphigoid

- EEC Syndrome

- Corneal Neovascularization

**Keywords:**

- Rare Eye Diseases

- Aniridia

- Neurotrophic Keratopathy

- Limbal Stem Cell Deficiency

- Ocular Graft-versus-host Disease

- Ocular Cicatricial Pemphigoid

- Corneal Neovascularization

- Molecular targets

- Cellular targets

- Genomic targets

- NK1R

- PBMC

- Substance P

- VEGF

- Blood

- Tear

- Impression cytology

- Cytokine

### Design Module

#### Design Info

**Observational Model:** CASE_CONTROL

**Time Perspective:** CROSS_SECTIONAL

#### Enrollment Info

**Count:** 274

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Label:** Patients

#### Arm Group 2

**Label:** Control group

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** To quantify the expression of molecular/cellular/genomic targets in the REDs and control group to detect statistically significant and clinically relevant differences.

**Time Frame:** Day 0 (enrollment day).

#### Secondary Outcomes

**Description:** 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.

**Measure:** 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.

**Time Frame:** Day 0 (enrollment day).

### Eligibility Module

**Eligibility Criteria:** 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.

**Healthy Volunteers:** True

**Maximum Age:** 99 Years

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**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.

### References Module

#### See Also Links

**Label:** European Commission, ERN-EYE: a European Reference Network dedicated to Rare Eye Diseases. Accessed 29 December 2021

**URL:** https://www.ern-eye.eu/ern-eye-a-european-reference-network-dedicated-to-rare-eye-diseases/

**Label:** European Blind Union, About Blindness and Partial Sight: Facts and Figures. Accessed 26 August 2022

**URL:** https://www.euroblind.org/about-blindness-and-partial-sight/facts-and-figures

**Label:** Restore Vision site

**URL:** https://restorevision-project.eu/

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000007154

- Term: Immune System Diseases

- ID: D000008679

- Term: Metaplasia

- ID: D000010335

- Term: Pathologic Processes

- ID: D000020969

- Term: Disease Attributes

- ID: D000012872

- Term: Skin Diseases, Vesiculobullous

- ID: D000012871

- Term: Skin Diseases

- ID: D000001327

- Term: Autoimmune Diseases

- ID: D000003316

- Term: Corneal Diseases

- ID: D000005128

- Term: Eye Diseases

- ID: D000005124

- Term: Eye Abnormalities

- ID: D000015785

- Term: Eye Diseases, Hereditary

- ID: D000007499

- Term: Iris Diseases

- ID: D000014603

- Term: Uveal Diseases

- ID: D000000013

- Term: Congenital Abnormalities

- ID: D000030342

- Term: Genetic Diseases, Inborn

- ID: D000003229

- Term: Conjunctival Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC26

- Name: Wounds and Injuries

- Abbrev: BC11

- Name: Eye Diseases

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M24518

- Name: Rare Diseases

- Relevance: HIGH

- As Found: Rare disease

- ID: M15241

- Name: Rupture

- Relevance: LOW

- As Found: Unknown

- ID: M8271

- Name: Eye Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9189

- Name: Graft vs Host Disease

- Relevance: HIGH

- As Found: Graft Versus Host Disease

- ID: M2921

- Name: Limbal Stem Cell Deficiency

- Relevance: HIGH

- As Found: Limbal Stem Cell Deficiency

- ID: M18907

- Name: Corneal Neovascularization

- Relevance: HIGH

- As Found: Corneal Neovascularization

- ID: M18337

- Name: Aniridia

- Relevance: HIGH

- As Found: Aniridia

- ID: M13301

- Name: Pemphigoid, Benign Mucous Membrane

- Relevance: HIGH

- As Found: Ocular Cicatricial Pemphigoid

- ID: M13302

- Name: Pemphigoid, Bullous

- Relevance: HIGH

- As Found: Pemphigoid

- ID: M12334

- Name: Neovascularization, Pathologic

- Relevance: HIGH

- As Found: Neovascularization

- ID: M22785

- Name: Lacerations

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11659

- Name: Metaplasia

- Relevance: LOW

- As Found: Unknown

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15675

- Name: Skin Diseases, Vesiculobullous

- Relevance: LOW

- As Found: Unknown

- ID: M4629

- Name: Autoimmune Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6539

- Name: Corneal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12

- Name: Congenital Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M8267

- Name: Eye Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M18339

- Name: Eye Diseases, Hereditary

- Relevance: LOW

- As Found: Unknown

- ID: M10531

- Name: Iris Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17351

- Name: Uveal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: M6453

- Name: Conjunctival Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T2832

- Name: Homologous Wasting Disease

- Relevance: HIGH

- As Found: Graft Versus Host Disease

- ID: T891

- Name: Bullous Pemphigoid

- Relevance: HIGH

- As Found: Pemphigoid

- ID: T400

- Name: Aniridia

- Relevance: HIGH

- As Found: Aniridia

- ID: T3914

- Name: Mucous Membrane Pemphigoid

- Relevance: HIGH

- As Found: Cicatricial Pemphigoid

- ID: T4191

- Name: Ocular Cicatricial Pemphigoid

- Relevance: HIGH

- As Found: Ocular Cicatricial Pemphigoid

- ID: T2039

- Name: EEC Syndrome

- Relevance: HIGH

- As Found: EEC Syndrome

- ID: T5824

- Name: Uveal Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000092423

- Term: Limbal Stem Cell Deficiency

- ID: D000016510

- Term: Corneal Neovascularization

- ID: D000015783

- Term: Aniridia

- ID: D000010390

- Term: Pemphigoid, Benign Mucous Membrane

- ID: D000010391

- Term: Pemphigoid, Bullous

- ID: D000006086

- Term: Graft vs Host Disease

- ID: D000009389

- Term: Neovascularization, Pathologic

- ID: D000035583

- Term: Rare Diseases

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M16161

- Name: Substance P

- Relevance: LOW

- As Found: Unknown

- ID: M17988

- Name: Neurokinin A

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
