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

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.

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.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease; Genetic Predisposition
• Intervention / Treatment: Other: biomarkers

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.

• Study Type: Observational
• Enrollment (Actual): 240

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80000
    • Amiens University & Hospital
  • Clermont FERRAND, France, 63000
    • Clermont ferrand University hospital
  • Le Kremlin Bicêtre, France
    • Aphp Kremlin Bicetre
  • Lille, France
    • CHRU,Hôpital Jeanne de Flandres
  • Lille, France
    • Hôpital Claude Huriez, CHRU
  • Nancy, France, 54000
    • Nancy University Hospital
  • Paris, France, 75000
    • APHP Necker
  • Paris, France, 75000
    • APHP Robert Debré
  • Paris, France, 75000
    • APHP St Antoine
  • Rouen, France, 76000
    • Rouen University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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).

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
case Crohn disease; 60 cases with Crohn's Disease	Other: biomarkers; fecal microbiota analysis antibodies in serum and saliva DNA polymorphisms; Other Names: Dysbiosis
first relative healthy; 2 healthy relatives per CD case (total 120)	Other: biomarkers; fecal microbiota analysis antibodies in serum and saliva DNA polymorphisms; Other Names: Dysbiosis
controls; 60 controls matched on gender and age with CD cases	Other: biomarkers; fecal microbiota analysis antibodies in serum and saliva DNA polymorphisms; Other Names: Dysbiosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Investigators: Principal Investigator: Corinne Gower-Rousseau, MD, PhD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2013
• Primary Completion (Actual): April 3, 2019
• Study Completion (Actual): April 3, 2019

Study Registration Dates

• First Submitted: June 29, 2016
• First Submitted That Met QC Criteria: July 4, 2016
• First Posted (Estimate): July 11, 2016

Study Record Updates

• Last Update Posted (Actual): October 11, 2019
• Last Update Submitted That Met QC Criteria: October 10, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Biomarkers; Crohn's Disease; Dysbiosis; Healthy relatives
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Disease Susceptibility; Genetic Predisposition to Disease
• Other Study ID Numbers: 2011_21; 2012-A00802-41 (Other Identifier: ID-RCB number, ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED