Clinical trial NCT02826330: Abnormal Fecal Microbiota in Healthy Subjects at High Risk for Crohn's Disease
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.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Crohn's Disease
Genetic Predisposition
Keywords: Crohn's Disease
Healthy relatives
Dysbiosis
Biomarkers
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
First posted: 2016-07-11
Enrollment: 240
Sex: ALL
Minimum age (years): 8
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: FAMILY_BASED
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Transversal multicentric French study on the microbiota in patients with Crohn's disease (n=60) and their first degree healthy relatives (n=120) and controls (n=60).

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Lachnospiraceae bacteria in stools within 3 groups
timeFrame: 1 YEAR
Secondary outcomes:
measure: Number of bacteria Firmicutes phylum (including Faecalibacterium prausnitzii and Clostridium Leptum) in stools within 3 groups
timeFrame: 1 year
measure: Define different genetic and serologic backgrounds within 3 groups
timeFrame: 1 year
measure: Quantify of bacteria with invasive properties (including AIEC) within 3 groups
timeFrame: 1 year
measure: Study of environmental risk factors within 3 groups
timeFrame: 1 year
Other outcomes:
Locations:
city: Amiens
country: France
facility: Amiens University & Hospital
city: Clermont FERRAND
country: France
facility: cLERMONT fERRAND University Hospital
city: Le Kremlin Bicêtre
country: France
facility: APHP Kremlin Bicêtre
city: Lille
country: France
facility: CHRU,Hôpital Jeanne de Flandres
city: Lille
country: France
facility: Hôpital Claude Huriez, CHRU
city: Nancy
country: France
facility: Nancy University Hospital
city: Paris
country: France
facility: Aphp Necker
city: Paris
country: France
facility: APHP Robert Debré
city: Paris
country: France
facility: Aphp St Antoine
city: Rouen
country: France
facility: Rouen University Hospital
Study officials:
affiliation: University Hospital, Lille
name: Corinne Gower-Rousseau, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: