- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05100823
Validation of Therapeutic Efficacy Targeting the Splicing Variants in Cystic Fibrosis and CFTR Pathologies (ONB-CFTR)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Anne Bergougnoux, PhD, PharmD
- Phone Number: +33 411759879
- Email: anne.bergougnoux@inserm.fr
Study Contact Backup
- Name: Magali Taulan-Cadars, PhD
- Phone Number: +33 411759846
- Email: magali.taulan@inserm.fr
Study Locations
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-
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Montpellier, France, 34090
- Recruiting
- Montpellier University Hospital
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Contact:
- Anne Bergougnoux, phD, PharmD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
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.
Specific non-inclusion criteria for rectal sampling:
- the subject has thrombocytopenia
- the subject has a bleeding disorder
- The patient has severe inflammation of the rectum.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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. |
Nasal epithelium brushing in intermediate turbinate using a specific curette following a local anesthesia with Xylocaine 5% nebulizer.
Forceps Biopsy Procedure (Servidoni et al., 2013) Only for volunteer patients included in the Montpellier center.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Restoration of the correctly spliced CFTR mRNA (full length) using specific ONB-CFTR (designed for one splicing variant).
Time Frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
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The increase will be assessed in comparison to oligonucleotide-control effect by using semi-quantitative fluorescent PCR.
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21 days after the air-liquid switch of epithelia (i.e. full differentiation)
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Restoration of the mature CFTR protein using specific ONB-CFTR (designed for one splicing variant).
Time Frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
|
The increase will be assessed in comparison to oligonucleotide-control effect by using western blot
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21 days after the air-liquid switch of epithelia (i.e. full differentiation)
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Restoration of CFTR channel function using specific ONB-CFTR (designed for one splicing variant).
Time Frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
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The increase will be assessed in comparison to oligonucleotide-control effect by using electrophysiological assays (Ussing chamber).
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21 days after the air-liquid switch of epithelia (i.e. full differentiation)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Restoration of the correctly spliced CFTR mRNA (full length) and mature CFTR protein and CFTR channel function using a pool of ONB-CFTR (a mix of specific ONB-CFTR).
Time Frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
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The increase will be assessed in comparison to oligonucleotide-control effect by using semi-quantitative fluorescent PCR, western blot and electrophysiological assays (Ussing chamber).
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21 days after the air-liquid switch of epithelia (i.e. full differentiation)
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Assessment of the amount of CFTR mRNA with normal splicing under the conditions tested.
Time Frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
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That parameter will be quantified in comparison to oligonucleotide-control effect by using quantitative PCR assays.
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21 days after the air-liquid switch of epithelia (i.e. full differentiation)
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Assessment of the amount of mature CFTR proteins under the conditions tested.
Time Frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
|
That parameter will be quantified in comparison to oligonucleotide-control effect by using western blot assays.
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21 days after the air-liquid switch of epithelia (i.e. full differentiation)
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Assessment of the CFTR channel activity under the conditions tested.
Time Frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
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That parameter will be quantified in comparison to oligonucleotide-control effect by using electrophysiological assays (Ussing chamber).
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21 days after the air-liquid switch of epithelia (i.e. full differentiation)
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Increase of CFTR channel function using ONB-CFTR and CFTR modulators (correctors and/or potentiators) under the conditions tested.
Time Frame: 21 days after the air-liquid switch of epithelia (i.e. full differentiation)
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The increase will be assessed in comparison to oligonucleotide-control effect by using electrophysiological assays (Ussing chamber).
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21 days after the air-liquid switch of epithelia (i.e. full differentiation)
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- RECHMPL20_0423
- 2020-A03529-30 (Other Identifier: ANSM)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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