Search for New Genetic Mutations Major Effect in Crohn's Disease

Completed

• Conditions: Crohn Disease
• Interventions: Genetic: genetic analysis; Biological: blood and stools samples

• Registration Number: NCT02851134
• Lead Sponsor: University Hospital, Lille

Brief Summary

This study highlight genetics mutations with major effect in Crohn's Disease (CD) by WES in individuals affected and healthy individuals from EPIMAD Inserm InVS registry families.

Detailed Description

The EPIMAD Registry covers a large area of Northern France (9 millions inhabitants) and collects all incident CD cases and data from CD multiplex families (families with 3 or more CD affected patients) in the Nord the Pas de Calais the Somme and the Seine Maritime. If the investigators could demonstrate that most CD cases from multiplex families were related to high frequency of NOD2 gene mutations, the investigators found some CD multiplex families without any NOD2 gene involvement. Thus in these families high prevalence of CD cases may rely on other major genetic susceptibility variant(s) that remain to be determined.

this clinical research Whole Exome Sequencing protocol, aiming to highlight genetics mutations with major effect in CD has been initiated.

This study is a familial genetic study with intra-familial controls. The genetics analyses are:

* Ascertain of no significant NOD2 mutation in the family members by Sanger DNA sequencing

* WES (CD patients and family controls unaffected subjects)

* Genotyping of all mutations found, case control and segregation analyses to validate their implication in CD.

Study Timeline

• Study Start: 2015-04
• Study First Submitted: 2016-06-07
• Study First Submitted QC: 2016-07-27
• Study First Posted: 2016-08-01
• Primary Completion: 2018-04
• Study Completion: 2018-04
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-26
• Last Update Posted: 2019-02-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Crohn disease subject
• EPIMAD family with, at least, 3 Crohn disease subjects

Exclusion Criteria

• Pregnant or lactating women

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
family control subject	genetic analysis	family control unaffected subject
Crohn disease subject	genetic analysis	Crohn disease affected subject
family control subject	blood and stools samples	family control unaffected subject
Crohn disease subject	blood and stools samples	Crohn disease affected subject

Primary Outcome Measures

Name	Time	Method
NOD2 gene status	8 months after recruiting	One of the main inclusion criteria is the absence in the family (and thus in the proband) of any NOD2 mutation that could be related with the high occurrence of Crohn's Disease in the family. So verification of the lack of CD related NOD2 gene mutation is a prerequisite to the inclusion of the family in the protocol. This is achieved by Sanger sequencing of all exons, exon-intron junctions and search for already described intronic mutations in the family proband.

Secondary Outcome Measures

Name	Time	Method
Whole Exome Sequencing	10 months after recruiting	Whole Exome Sequencing will be performed in every subject from all families. All genetic variants will be filtered with bioinformatic tools. Genetic variants with putative biological effect, presents in affected CD patients and absents in their unaffected relatives will be further investigated (i.e. cosegregation with the disease, involvement in a given pathway....). This study remains a "pilot study" to identify genetic variants that may be involved in Crohn's Disease.

Trial Locations

Locations (1)

CHRU, Hôpital Claude Huriez; 🇫🇷 Lille, France