ClinicalTrials.gov
ClinicalTrials.gov Menu

Identification of Epigenetic Biomarkers Allowing to Predict the Evolution of Lung Disease Severity in Cystic Fibrosis, in Order to Improve Patient Follow-up and to Move Toward Personalized Medicine (MethylBiomark)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02976714
Recruitment Status : Recruiting
First Posted : November 29, 2016
Last Update Posted : May 12, 2017
Sponsor:
Information provided by (Responsible Party):
University Hospital, Montpellier

Brief 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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Other: spontaneous sputum Not Applicable

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  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Identification of Predictive Epigenetic Biomarkers of Lung Disease Severity in Cystic Fibrosis
Actual Study Start Date : December 12, 2016
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.





Primary Outcome Measures :
  1. DNA methylation [ Time Frame: at time of inclusion ]
    Spontaneous expectoration at baseline

  2. DNA methylation [ Time Frame: 6 months ]
    Spontaneous expectoration at 6 months

  3. DNA methylation [ Time Frame: 12 months ]
    Spontaneous expectoration at 12 months

  4. DNA methylation [ Time Frame: 18 months ]
    Spontaneous expectoration at 18 months



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   12 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02976714


Contacts
Contact: Albertina De Sario, PhD 4 11 75 98 63 ext 33 albertina.de-sario@inserm.fr
Contact: Davide CAIMMI, MD

Locations
France
Uhmontpellier Recruiting
Montpellier, France, 34295
Contact: Albertina De Sario         
Sponsors and Collaborators
University Hospital, Montpellier
Investigators
Principal Investigator: Davide CAIMMI University Hospital, Montpellier

Responsible Party: University Hospital, Montpellier
ClinicalTrials.gov Identifier: NCT02976714     History of Changes
Other Study ID Numbers: UF9745
First Posted: November 29, 2016    Key Record Dates
Last Update Posted: May 12, 2017
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by University Hospital, Montpellier:
Cystic Fibrosis
Lung disease
DNA methylation
Predictive biomarkers

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Lung Diseases
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases