Identification of Predictive Epigenetic Biomarkers of Lung Disease Severity in Cystic Fibrosis (MethylBiomark)

March 27, 2026 updated by: University Hospital, Montpellier
The general aims of this project are (i) to identify predictive epigenetic biomarkers of lung disease severity in Cystic Fibrosis, (ii) to characterize a non-invasive cellular model, spontaneous sputum, for the analysis of these epigenetic biomarkers, (iii) to analyze the variations in DNA methylation for a same patient over time.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cystic Fibrosis (CF) is an autosomal recessive disease resulting from mutations in the CFTR gene. CFTR encodes a chloride channel, mainly expressed at the apical membrane of epithelial cells. CFTR dysfunction induces mucus thickening, causing multiple disorders in respiratory, digestive and reproductive tracts. In CF patients, lung disease is the main cause of morbidity and mortality, and its severity is variable among CF patients, even among those with the same genotype. This clinical variability depends on two factors: genetic (complex alleles of CFTR gene and modifier genes) and environmental factors. Genetic factors have been largely explored, and several modifier genes have been identified. By contrast, environmental factors are still poorly known. It is well established that environmental factors modify the phenotype by acting on epigenetic marks (i.e. DNA methylation, histone modification) present in the genome. Epigenetic modifications regulate and modulate gene expression.

In a previous we profiled DNA methylation genome-wide in nasal epithelial cell samples from 32 CF patients and 24 healthy controls. CF patients homozygous for the p.Phe508del mutation and >18-years-old were stratified according to the lung disease severity. Through this study, we identified 187 genomic regions (CpG dinucleotides) differentially methylated between CF patients with mild lung disease and CF patients with severe lung disease. The present project aims at identifying predictive epigenetic biomarkers of lung disease severity, among these 187 regions. While the previous study was carried out on genomic DNA extracted from nasal epithelial cells, in the present project we will use a non-invasive model: spontaneous sputum.

Hypothesis: some differentially methylated genomic regions between mild and severe CF patients can be used as predictive epigenetic biomarkers of lung disease severity in cystic fibrosis.

Objectives: (i) to identify predictive epigenetic biomarkers of lung disease severity among the differentially methylated genomic regions between mild and severe CF patients, (ii) to characterize a non-invasive cellular model, spontaneous sputum, for the analysis of epigenetic biomarkers of lung disease severity in CF, (iii) to analyze the variations in DNA methylation for a same patient over time (at time of inclusion, 6 months, 12 months and 18 months)

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Montpellier, France, 34295
        • Uhmontpellier

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • free and informed consent obtained, and consent signed
  • subject covered by a state insurance scheme
  • women and men aged 12 to 30
  • subject affected by cystic fibrosis, carrier of two severe mutations in trans (in the same allele) in the CFTR gene
  • subject able to realize a spirometry before and during the study

Exclusion Criteria:

  • subject in an exclusion period of a previous study
  • subject placed under judicial protection, guardianship or supervision
  • impossibility to give informed information to the subject
  • subject who does not read fluently French
  • pregnancy
  • breastfeeding
  • transplanted subject

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: CF patients
CF patients carry a spontaneous sputum that is made in the context of bronchial drainage sessions conducted as part of usual care.
Other: spontaneous sputum

CF patients carry a spontaneous sputum that is made in the context of bronchial drainage sessions conducted as part of usual care (inclusion, 6 months, 12 months, 18 months).

The collection of spontaneous sputum is carried out within the bronchial drainage sessions, which are routinely performed at each visit. The spontaneous sputum is collected in a sterile container. In order not to contaminate the sputum with buccal epithelial cells will be asked patients to rinse the mouth before expectorate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DNA methylation
Time Frame: at time of inclusion
Spontaneous expectoration at baseline
at time of inclusion
DNA methylation
Time Frame: 6 months
Spontaneous expectoration at 6 months
6 months
DNA methylation
Time Frame: 12 months
Spontaneous expectoration at 12 months
12 months
DNA methylation
Time Frame: 18 months
Spontaneous expectoration at 18 months
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Montpellier

Investigators

  • Principal Investigator: Davide CAIMMI, University Hospital, Montpellier

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 12, 2016

Primary Completion (Actual)

July 13, 2021

Study Completion (Actual)

July 13, 2021

Study Registration Dates

First Submitted

November 8, 2016

First Submitted That Met QC Criteria

November 24, 2016

First Posted (Estimated)

November 29, 2016

Study Record Updates

Last Update Posted (Actual)

April 2, 2026

Last Update Submitted That Met QC Criteria

March 27, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RECHMPL16_0256

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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