Cystic FibrosisNCT03670472
Correction of Nonsense Mutations in Cystic Fibrosis
An observational study of Cystic Fibrosis, run by University Hospital, Lille at 8 sites in France.
Trial summary
The presence of a nonsense mutation leads to the rapid degradation of the carrier mRNA mutation by a mechanism called NMD (nonsense-mediated mRNA decay) [6, 13]. There are currently 3 main strategies at least for correcting nonsense mutations: exon skipping, inhibition of NMD and nonsense mutation readthrough. Read more about this study
- Who is it for?
- Ages 8 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- smear of nasal fossae
- How many people
- 85 participants
- Where
- 8 sitesFrance
- Study dates
- 3 Feb 2016to Jan 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with cystic fibrosis and carry a nonsense mutation on the 2 alleles of the gene coding for the CFTR channel.
Who may be able to join
- Male / female adults and minors aged 8 years and over
- Patients with cystic fibrosis and carry a nonsense mutation on the 2 alleles of the gene coding for the CFTR channel.
- Patients whose genotype of patients concerning the CFTR gene is known.
- Patients with social security
- Major patients who have given their consent
- Minor patients with parental authorization
Who cannot join
- Patients who have a mutation other than nonsense in the CFTR gene
- Patients whose CFTR gene was not sequenced on the 2 alleles
- Patients not wishing to participate in this study or persons not giving or not able to give consent.
- Pregnant or lactating women
- Patients under curatorship or guardianship
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Fabrice Lejeune, PhD contact
8 sites in 1 country
France8 sites, 8 recruiting
- Recruiting
Camsp Chu Amiens
Amiens
- Recruiting
Hopital Femme Mere Enfant - Hcl - Bron
Bron
- Recruiting
Hôpital Calmette,CHU
Lille
Anne Prévotat, MD
- Recruiting
Aphm Hopital La Timone - Marseille
Marseille
- Recruiting
Chu Montpellier
Montpellier
- Recruiting
Cmp Enfants Aphp Robert Debre - Paris
Paris
- Recruiting
Hu Paris Centre Site Cochin Aphp - Paris 14
Paris
- Recruiting
Hopitaux Universitaires de Strasbour
Strasbourg
About this study
Official title: Optimization of Correcting Molecules of Nonsense Mutations in Epithelial Cells of the Upper Airways of Patients With Cystic Fibrosis With Nonsense Mutations in the CFTR Gene
The presence of a nonsense mutation leads to the rapid degradation of the carrier mRNA mutation by a mechanism called NMD (nonsense-mediated mRNA decay) [6, 13]. There are currently 3 main strategies at least for correcting nonsense mutations: exon skipping, inhibition of NMD and nonsense mutation readthrough.
In the laboratory, we developed a strategy for correcting nonsense mutations combining inhibition of NMD and activation of translecture. For this purpose, we have constructed screening systems to identify NMD-inhibiting and/or readthrough enhancers. The molecules thus identified are then tested on cell lines and in murine models carrying a nonsense mutation.
Read more
One of our goals is to select a set of molecules that can correct effectively nonsense mutations. For this we have to test these molecules on a great diversity of nonsense mutations.
This work will:
- determine if we can correct all the nonsense mutations tested with at least one of our molecules
- determine what is common within a group of mutations corrected by a given molecule
- be able to assign the parameters that make one mutation is corrected by one molecule and not or little by another.
This study will therefore improve our theoretical knowledge on the recognition of premature stop codons but also to propose therapeutic approaches for the correction of nonsense mutations of the CFTR gene in cystic fibrosis in a targeted way for a patient.
- Conditions
- Cystic Fibrosis
- Being tested
- smear of nasal fossae
- Keywords
- Cystic fibrosis, nonsense mutations, CFTR gene, nasal epithelial cells, nonsense mutation readthrough
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
smear of nasal fossaeOther
1 smear of nasal fossae during a usual or scheduled visit
What is being measured
The primary outcome is the main question the study is designed to answer.
Transport of iodide ions through the CEVAS membrane
Patient cells with be cultured in BEGM (Lonza) medium and incubated with corrector of nonsense mutations for 20 hours and with a fluorescent molecule called SPQ (for 6-methoxy-N-3'-sulfopropylquinolinium). Iodine can bind SPQ and will quench the SPQ fluorescence. Nitrates bind SPQ without quenching SPQ fluorescence. By placing patient cells first into an iodine-rich medium to quench the SPQ fluorescence and second into a nitrate-rich medium, we will be able to measure the level of functional CFTR protein present in these cells by measuring the re-apparition of fluorescence using fluorimeter. Indeed, nitrate will be able to replace iodine on SPQ without quenching SPQ fluorescence only if iodine exits cells through CFTR channels. This assay allows determining whether a corrector of nonsense mutation is able to lead to the synthesis of functional CFTR protein
Measured: less than 48hrs after the collect.
Secondary outcomes (2)
Immortalization of patient cells
Immortalization of patient cells will be attempted by transfection of construct expressing the origin-of-replication defective SV40 as described in Gruenert et al.,2004
Measured: an average 12 months
Expression of the CFTR gene at the mRNA and protein level
Measured: less than 1 week.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2018
- Study start3 Feb 2016
- Primary completionJan 2030 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University Hospital, LilleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 85 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Lille
- Sponsor type
- University, hospital or other
- Collaborators
- Vaincre la Mucoviscidose
- Responsible party
- Sponsor
- Investigators
- Anne Prévotat, MD, Principal investigator, University Hospital, Lille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03670472
- Sponsor's protocol ID
- 2013_59
- Other IDs
- 2014-A01236-41
- Status last verified
- May 2026
- First submitted
- 1 Aug 2018
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimization of Correcting Molecules of Nonsense Mutations in Epithelial Cells of the Upper Airways of Patients With Cystic Fibrosis With Nonsense Mutations in the CFTR Gene
- ClinicalTrials.gov ID
- NCT03670472
- Acronym / sponsor ID
- 2013_59
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic fibrosis, nonsense mutations, CFTR gene, nasal epithelial cells, nonsense mutation readthrough
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 85 participants (estimated)
- Lead sponsor
- University Hospital, LilleUniversity, hospital or other
- Collaborators
- Vaincre la Mucoviscidose
- Study start
- 3 Feb 2016 (actual)
- Primary completion
- Jan 2030 (estimated)
- Study completion
- Jan 2030 (estimated)
- First posted
- 13 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The presence of a nonsense mutation leads to the rapid degradation of the carrier mRNA mutation by a mechanism called NMD (nonsense-mediated mRNA decay) [6, 13]. There are currently 3 main strategies at least for correcting nonsense mutations: exon skipping, inhibition of NMD and nonsense mutation readthrough.
In the laboratory, we developed a strategy for correcting nonsense mutations combining inhibition of NMD and activation of translecture. For this purpose, we have constructed screening systems to identify NMD-inhibiting and/or readthrough enhancers. The molecules thus identified are then tested on cell lines and in murine models carrying a nonsense mutation.
One of our goals is to select a set of molecules that can correct effectively nonsense mutations. For this we have to test these molecules on a great diversity of nonsense mutations.
This work will:
- determine if we can correct all the nonsense mutations tested with at least one of our molecules
- determine what is common within a group of mutations corrected by a given molecule
- be able to assign the parameters that make one mutation is corrected by one molecule and not or little by another.
This study will therefore improve our theoretical knowledge on the recognition of premature stop codons but also to propose therapeutic approaches for the correction of nonsense mutations of the CFTR gene in cystic fibrosis in a targeted way for a patient.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with cystic fibrosis and carry a nonsense mutation on the 2 alleles of the gene coding for the CFTR channel.
Key inclusion criteria (6 listed)
- Male / female adults and minors aged 8 years and over
- Patients with cystic fibrosis and carry a nonsense mutation on the 2 alleles of the gene coding for the CFTR channel.
- Patients whose genotype of patients concerning the CFTR gene is known.
- Patients with social security
- Major patients who have given their consent
Key exclusion criteria (5 listed)
- Patients who have a mutation other than nonsense in the CFTR gene
- Patients whose CFTR gene was not sequenced on the 2 alleles
- Patients not wishing to participate in this study or persons not giving or not able to give consent.
- Pregnant or lactating women
- Patients under curatorship or guardianship
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| smear of nasal fossae1 smear of nasal fossae during a usual or scheduled visit | Other | – |
Primary outcome
Transport of iodide ions through the CEVAS membrane
Time frame: less than 48hrs after the collect.
Patient cells with be cultured in BEGM (Lonza) medium and incubated with corrector of nonsense mutations for 20 hours and with a fluorescent molecule called SPQ (for 6-methoxy-N-3'-sulfopropylquinolinium). Iodine can bind SPQ and will quench the SPQ fluorescence. Nitrates bind SPQ without quenching SPQ fluorescence. By placing patient cells first into an iodine-rich medium to quench the SPQ fluorescence and second into a nitrate-rich medium, we will be able to measure the level of functional CFTR protein present in these cells by measuring the re-apparition of fluorescence using fluorimeter. Indeed, nitrate will be able to replace iodine on SPQ without quenching SPQ fluorescence only if iodine exits cells through CFTR channels. This assay allows determining whether a corrector of nonsense mutation is able to lead to the synthesis of functional CFTR protein
2 secondary outcomes
Immortalization of patient cells
Time frame: an average 12 months
Expression of the CFTR gene at the mRNA and protein level
Time frame: less than 1 week.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Fabrice Lejeune, PhD contact
Anne Prévotat, MD principal investigator
University Hospital, Lille
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cystic Fibrosis, run by University Hospital, Lille at 8 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anne Prévotat, MD (03 20 44 59 48 ext. +33, anne.prevotat@chru-lille.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Transport of iodide ions through the CEVAS membrane (time frame: less than 48hrs after the collect.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.