Clinical trial NCT02884622: DNA Methylation and Lung Disease in Cystic Fibrosis
Official title: DNA Methylation and Lung Disease in Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cystic Fibrosis
Keywords: Lung disease
Epigenetics
DNA methylation
Modifier genes
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
Collaborators: name: Vaincre la Mucoviscidose
name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2016-08-31
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Lung disease progression is variable among cystic fibrosis (CF) patients and depends on DNA mutations in the CFTR gene, polymorphic variations in disease-modifier genes and environmental exposure. The contribution of genetic factors has been extensively investigated, whereas the mechanism whereby environmental factors modulate the lung disease is unknown. Because these factors can affect the epigenome, investigators hypothesized that DNA methylation variations at disease-modifier genes modulate the lung function in CF patients.

Detailed description: Lung disease progression is variable among cystic fibrosis (CF) patients and depends on DNA mutations in the CFTR gene, polymorphic variations in disease-modifier genes and environmental exposure. The contribution of genetic factors has been extensively investigated, whereas the mechanism whereby environmental factors modulate the lung disease is unknown. Because these factors can affect the epigenome, investigators hypothesized that DNA methylation variations at disease-modifier genes modulate the lung function in CF patients.

The investigators analyzed DNA methylation levels in the promoter of fourteen lung disease-modifier genes and showed that DNA methylation levels are altered in nasal epithelial and blood cell samples from CF patients. This study disclosed slightly, but significantly differentially methylated regions that collectively may modulate lung disease severity. It also highlighted that complex relationships between genetic and epigenetic factors contribute to the phenotypic variability of CF patients.

Eligibility criteria: Inclusion Criteria:

* \>18 years old
* homozygous for the F508del mutation

Exclusion Criteria:

* subjects who have an active CF exacerbation or a recent viral infection on the day of biological samples collection;
* pregnant women;
* patients who are included in interventional medical trials;
* patients who had lung transplantation.

Primary outcomes:
measure: DNA methylation levels (chemical changes)
timeFrame: D0 (day of inclusion)
Secondary outcomes:
Other outcomes:
Locations:
city: Montpellier
country: France
facility: UHMontpellier
Study officials:
affiliation: University Hospital, Montpellier
name: Raphaël CHIRON, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Magalhaes M, Tost J, Pineau F, Rivals I, Busato F, Alary N, Mely L, Leroy S, Murris M, Caimmi D, Claustres M, Chiron R, De Sario A. Dynamic changes of DNA methylation and lung disease in cystic fibrosis: lessons from a monogenic disease. Epigenomics. 2018 Aug;10(8):1131-1145. doi: 10.2217/epi-2018-0005. Epub 2018 Jul 27.