Validation of Therapeutic Efficacy Targeting the Splicing Variants in Cystic Fibrosis and CFTR Pathologies

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-30

Study Completion Date

2025-02-17

Brief Summary

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Cystic Fibrosis, an inherited autosomal recessive disease, arises from mutations in the CFTR gene. For intronic mutations affecting splicing events, oligonucleotides therapy has the potential to restore the production of the full length CFTR protein. Recent scientific research has demonstrated the potential of this approach to restore full length mRNA CFTR in in vitro human airway cells. The study aims to validate the therapeutic efficacy of oligonucleotide blockers (ONB) that target splicing defects associated to splicing variants in epithelia obtained from patients with Cystic Fibrosis and CFTR-related disorders.

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Detailed Description

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The study will include patients with various CFTR genotypes. The assessment of ONB (named ONB-CFTR) will be performed using an air-liquid interface model of airway epithelium, developed from nasal cells of patients, without or with a combination of existing CFTR modulators, depending on the patient' genotype.

This study will also aim to build a local biobank of rectal organoids from patients (only from Montpellier, France) carrying rare CFTR disease-causing variants.

Conditions

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Cystic Fibrosis CFTR Gene Mutation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Nasal cells sampling and/or rectal biospy

Depending of the patient' genotype, specific ONB-CFTR (50 nM) will be incubated at the apical face of in vitro epithelium, alone and in combination with CFTR modulators. Efficacy of ONB will be compared to a condition with oligonucleotide control incubation.

Rectal biopsies from volunteer patients were stored as a bio-bank of organoids.

Group Type EXPERIMENTAL

Nasal cells sampling

Intervention Type PROCEDURE

Nasal epithelium brushing in intermediate turbinate using a specific curette following a local anesthesia with Xylocaine 5% nebulizer.

Rectal biopsy sampling

Intervention Type PROCEDURE

Forceps Biopsy Procedure (Servidoni et al., 2013) Only for volunteer patients included in the Montpellier center.

Interventions

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Nasal cells sampling

Nasal epithelium brushing in intermediate turbinate using a specific curette following a local anesthesia with Xylocaine 5% nebulizer.

Intervention Type PROCEDURE

Rectal biopsy sampling

Forceps Biopsy Procedure (Servidoni et al., 2013) Only for volunteer patients included in the Montpellier center.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* The subject must have given their free and informed consent and signed the consent
* The subject must be affiliated or beneficiary of a health insurance plan Women and men are included
* The patient is at least 12 years old.
* The patient has cystic fibrosis or a CFTR pathology and therefore carries two mutations (with at least one mutation affecting splicing) in the CFTR gene.
* Patients who volunteer for rectal biopsy collection (only from Montpellier University Hospital) must be at least 18 years old.

* the subject has thrombocytopenia
* the subject has a bleeding disorder
* The patient has severe inflammation of the rectum.

Exclusion Criteria

* The subject is in a period of exclusion determined by a previous study.
* The subject is under judicial protection, under guardianship or under curatorship
* The subject does not accept to sign consent
* It turns out to be impossible to give informed information to the subject
* The subject does not read the French language fluently
* The subject is a pregnant or breastfeeding woman
* The subject has porphyria, or has hepatic insufficiency, or suffers from epilepsy, or suffers from conduction disorders, or suffers from severe heart failure, has a cons-indication to the use of a local anesthetic spray.

Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No