Abnormal Fecal Microbiota in Healthy Subjects at High Risk for Crohn's Disease

Crohn's Disease Clinical Trial

— MAGIC  

Official title:

Evidence of Abnormal Fecal Microbiota in Healthy Subjects at High Risk for Crohn's Disease: Family Studies and Relations With a Particular Genetic Profile and Serological. Comparison of Affected Individuals, Their Siblings and Healthy Controls.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02826330
• Other study ID #: 2011_21
• Secondary ID: 2012-A00802-41
• Status: Completed
• Start date: October 3, 2013
• Est. completion date: April 3, 2019

Study information

• Verified date: October 2019
• Source: University Hospital, Lille
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Transversal multicentric French study on the microbiota in patients with Crohn's disease and their first degree healthy relatives The primary objective is the comparison of microbiota between patients with CD, healthy controls non genetically linked and first degree healthy relatives of patients with CD.

Description:

Crohn's disease is a chronic inflammatory bowel disease associating flares and remission periods. Its etiology is unknown and there are no specific therapy. CD affects young patients and has a major impact on quality of life. There are few population-based studies and there are about 2.5 million affected patients in Europe and North America. From data from EPIMAD Registry the number of affected patients in France should be 200 000. The Crohn's disease pathogenesis is bad known; It coul be the results of the activation of the gastro-intestinal immune system toward gut microbiota in genetically susceptible hosts. In CD patients there is an important ecologic modification of the flora with an excess of Bacteroidetes and Proteobacteria and a decrease of anti inflammatory bacteria (Firmicutes). In ileum of CD patients a specific E Coli (adherent and invasive E Colo) is found in two thirds of cases.The presence of this AIEC seems to be associated to the variant NOD2 (results from our team in multiplex families).

In a family with at least 1 patient with CD, the healthy first degree relatives present a high risk (* 10) to also develop a CD.

The primary objective is the comparison of microbiota between patients with CD, healthy controls non genetically linked and first degree healthy relatives of patients with CD. The first endpoint is the Lachnospiraceae rates in each group.

The secondary objectives are :

1. the search for an association between bacterial dysbiosis and different genetic backgrounds in patients with CD, their first degree healthy relatives and controls.

2. the quantification of potential invasive bacteria with invasive properties (E. coli including adherent-invasive E. coli, Shigella, Salmonella, Yersinia, Campylobacter), and fecal fungal flora (Candida albicans, in particular) and their association with genetic and serological profiles in patients with CD, their healthy relatives and control subjects.

3. a study of environmental risk factors using a questionnaire to be submitted to CD patients, their healthy relatives and control subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: April 3, 2019
• Est. primary completion date: April 3, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 50 Years

Eligibility

Inclusion Criteria:

Patient with Crohn's disease

• Patient > 18 years old

• Having at least one first degree health relative

• OK to participate to the project

First degree healthy relatives

• specific clinical questionnaire and dosing fecal calprotectin to ensure the absence of inflammatory pathology.

• OK to participate to the project

Exclusion Criteria:

• Intestinal resection.

• Pregnant or breastfeeding woman.

• subject under guardianship

• subject does not speak French

• person unable to speak

• taking antibiotics or bowel preparation will push 6 weeks stool specimens, after cessation treatments.

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease
• Disease Susceptibility
• Genetic Predisposition
• Genetic Predisposition to Disease

Intervention

Other:
• biomarkers
fecal microbiota analysis antibodies in serum and saliva DNA polymorphisms

Locations

Country	Name	City	State
France	Amiens University & Hospital	Amiens
France	cLERMONT fERRAND University Hospital	Clermont FERRAND
France	APHP Kremlin Bicêtre	Le Kremlin Bicêtre
France	CHRU,Hôpital Jeanne de Flandres	Lille
France	Hôpital Claude Huriez, CHRU	Lille
France	Nancy University Hospital	Nancy
France	Aphp Necker	Paris
France	APHP Robert Debré	Paris
France	Aphp St Antoine	Paris
France	Rouen University Hospital	Rouen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Lille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Lachnospiraceae bacteria in stools within 3 groups	After extraction DNA, microbiota will be studied via study of ribosomal DNA 16S using quantitative PCR and pyroséquençage	1 YEAR
Secondary	Number of bacteria Firmicutes phylum (including Faecalibacterium prausnitzii and Clostridium Leptum) in stools within 3 groups	After extraction DNA, microbiota will be studied via study of ribosomal DNA 16S using quantitative PCR and pyroséquençage	1 year
Secondary	Define different genetic and serologic backgrounds within 3 groups	Genetic analysis will include 380 genetic variants génétiques that will be genotyped including classic variants involved in CD: variants or mutations of NOD2, NOD1, IL23R, ATG16L1, DGL5, TNF, IL6, NFKB1... genes. Serological analysis will included anti-OmpC, anti-I2 and ASCA auto antibodies.	1 year
Secondary	Quantify of bacteria with invasive properties (including AIEC) within 3 groups	Amplify bacterial DNA of Salmonella Typhi (amplification of ITS area specific of ARNr 16S-23S gene. For AIEC, using of qPCR methods based on chuA and yjaA genes.	1 year
Secondary	Study of environmental risk factors within 3 groups	Specific questionnaire on environmental risk factors including vaccination, antibiotic use, ionfections, Home facilities and Diet befor the CD diagnosis	1 year