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

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ClinicalTrials.gov Identifier: NCT02826330
Recruitment Status : Completed
First Posted : July 11, 2016
Last Update Posted : October 11, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Lille

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.

Condition or disease Intervention/treatment
Crohn's Disease Genetic Predisposition 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.

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Study Type : Observational [Patient Registry]
Actual Enrollment : 240 participants
Observational Model: Family-Based
Time Perspective: Cross-Sectional
Target Follow-Up Duration: 1 Year
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.
Actual Study Start Date : October 3, 2013
Actual Primary Completion Date : April 3, 2019
Actual Study Completion Date : April 3, 2019

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: Dysbiosis




Primary Outcome Measures :
  1. Percentage of Lachnospiraceae bacteria in stools within 3 groups [ Time Frame: 1 YEAR ]
    After extraction DNA, microbiota will be studied via study of ribosomal DNA 16S using quantitative PCR and pyroséquençage


Secondary Outcome Measures :
  1. Number of bacteria Firmicutes phylum (including Faecalibacterium prausnitzii and Clostridium Leptum) in stools within 3 groups [ Time Frame: 1 year ]
    After extraction DNA, microbiota will be studied via study of ribosomal DNA 16S using quantitative PCR and pyroséquençage

  2. Define different genetic and serologic backgrounds within 3 groups [ Time Frame: 1 year ]
    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.

  3. Quantify of bacteria with invasive properties (including AIEC) within 3 groups [ Time Frame: 1 year ]
    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.

  4. Study of environmental risk factors within 3 groups [ Time Frame: 1 year ]
    Specific questionnaire on environmental risk factors including vaccination, antibiotic use, ionfections, Home facilities and Diet befor the CD diagnosis


Biospecimen Retention:   Samples With DNA
Blood, saliva, stools


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Ages Eligible for Study:   8 Years to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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).
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02826330


Locations
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France
Amiens University & Hospital
Amiens, France, 80000
cLERMONT fERRAND University Hospital
Clermont FERRAND, France, 63000
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, 54000
Aphp Necker
Paris, France, 75000
APHP Robert Debré
Paris, France, 75000
Aphp St Antoine
Paris, France, 75000
Rouen University Hospital
Rouen, France, 76000
Sponsors and Collaborators
University Hospital, Lille
Investigators
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Principal Investigator: Corinne Gower-Rousseau, MD, PhD University Hospital, Lille
Additional Information:

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Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT02826330    
Other Study ID Numbers: 2011_21
2012-A00802-41 ( Other Identifier: ID-RCB number, ANSM )
First Posted: July 11, 2016    Key Record Dates
Last Update Posted: October 11, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by University Hospital, Lille:
Crohn's Disease
Healthy relatives
Dysbiosis
Biomarkers
Additional relevant MeSH terms:
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Crohn Disease
Disease Susceptibility
Genetic Predisposition to Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Disease Attributes
Pathologic Processes