Identification of Predictive Epigenetic Biomarkers of Lung Disease Severity in Cystic Fibrosis

Cystic Fibrosis Clinical Trial

— MethylBiomark  

Official title:

Identification of Predictive Epigenetic Biomarkers of Lung Disease Severity in Cystic Fibrosis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02976714
• Other study ID #: UF9745
• Status: Active, not recruiting
• Phase: N/A
• Start date: December 12, 2016
• Est. completion date: December 2021

Study information

• Verified date: October 2021
• Source: University Hospital, Montpellier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Lung Diseases

Intervention

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.

Locations

Country	Name	City	State
France	Uhmontpellier	Montpellier

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DNA methylation	Spontaneous expectoration at baseline	at time of inclusion
Primary	DNA methylation	Spontaneous expectoration at 6 months	6 months
Primary	DNA methylation	Spontaneous expectoration at 12 months	12 months
Primary	DNA methylation	Spontaneous expectoration at 18 months	18 months