Characterization of the Intestinal Microbiota in Patients With Inflammatory Bowel Disease and/or Spondyloarthritis and Study of the Impact of an Anti-TNF Alpha Therapy (MIST)

May 25, 2022 updated by: University Hospital, Bordeaux

Spondyloarthritis and inflammatory bowel diseases are common diseases, frequently met together in overlap syndromes. Their physiopathology remains puzzling. A strong role of gut microbiota has been recently put forward to explain the development of inflammatory bowel diseases, and is suspected to play an important role in rheumatoid diseases. Anti-Tumor Necrosis Factor (anti-TNF) alpha are effective and safe drugs in the treatment of both digestive and rheumatoid inflammatory diseases. The way they work is unclear, and the clinical response to this treatment is variable. A better understanding of the pathophysiology of inflammatory bowel diseases and of the action of anti-TNF alpha is essential to an optimized care.

Our hypothesis is that the efficacy of anti-TNF alpha in spondyloarthritis and in inflammatory bowel diseases is at least partly due to its restoring action of homeostasis at the interface between gastrointestinal mucosa and intestinal microbiota, either by primary action on the digestive epithelium, allowing it to regain its control and tolerance functions toward mucosal microbiota, either by direct action on the intestinal microbiota, via an inter-reigns regulation.

The main objective of our study is to assess quantitative and qualitative changes in fecal microbiota before (D0) and 3 months after initiation of anti-TNF alpha.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigators propose to conduct an exploratory study, on 10 spondyloarthritis and 20 inflammatory bowel diseases patients (10 Crohn's disease and 10 ulcerative colitis (UC), in which a first anti-TNF alpha treatment is indicated. At D0 and M3, intestinal microbiota will be studied by DNA16S sequencing and qPCR, via a stool sampling. Volatile Organic Compounds (VOCs) profile will be obtained by mass spectrometry. Blood lymphocytes profile will be obtained by flux cytometry. In addition, a colonoscopy will be performed at D0 for UC patients, with an endoscopic and histological assessment. A second short colonoscopy will be performed for UC patients at M3. At each time, clinical assessment will be performed.

A mirror group of 10 spondyloarthritis and 20 inflammatory bowel diseases patients (10 Crohn's disease and 10 ulcerative colitis), in which an "all but anti-TNF alpha or biotherapy" treatment is indicated will be included to distinguish the specific effects on microbiota of anti-TNF alpha.

12 patients by group will be included at M0 by anticipating that some patients will stop their treatment between M0 and M3, and consequently will be excluded from M3 sampling and from final analysis. Final analysis will be performed on 10 patients by group.

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Pessac, France
        • CHU de Bordeaux - service d'Hépato-gastroentérologie

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients aged over 18 years

  • Patients with the following conditions :

    • Ulcerative colitis (UC) fulfilling the ECCO criteria
    • Crohn's disease (CD) fulfilling the ECCO criteria
    • Axial or peripheral spondyloarthritis (SpA) fulfilling the Assessment of SpondyloArthritis (ASAS) criteria
  • Patients naïve to anti-TNF alpha, justifying the initiation of an anti-TNF alpha treatment according to current guidelines (ECCO Inflammatory bowel disease (IBD) recommendations, the recommendations of the French Society of Rheumatology for SpA)
  • Patients agreeing to sign the informed consent

Exclusion Criteria:

  • Patient with an inflammatory disease other than UC, CD or SpA
  • History of bowel resection or digestive stoma
  • Taking antibiotics in the three months preceding the stool collection
  • Patients with contraindication to treatment
  • Pregnancy or breast feeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patients with anti-TNF alpha
12 spondyloarthritis and 24 inflammatory bowel diseases patients (12 Crohn's disease and 12 ulcerative colitis), in which a first anti-TNF alpha treatment is indicated.
Other: blood sample
14 ml whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation
Other: stool samples
Study of the fecal microbiota
Other: food questionnaire
food questionnaire on the seven days before the collection
Other: colonoscopy
Only for patients with ulcerative colitis (in routine care)
Other: VOCs profile
Volatile Organic Compounds (VOCs) profile obtained by mass spectrometry
Active Comparator: mirror group
A mirror group of 12 spondyloarthritis and 24 inflammatory bowel diseases patients (12 Crohn's disease and 12 ulcerative colitis), in which an "all but anti-TNF alpha or biotherapy" treatment is indicated will be included to distinguish the specific effects on microbiota of anti-TNF alpha.
Other: blood sample
14 ml whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation
Other: stool samples
Study of the fecal microbiota
Other: food questionnaire
food questionnaire on the seven days before the collection
Other: colonoscopy
Only for patients with ulcerative colitis (in routine care)
Other: VOCs profile
Volatile Organic Compounds (VOCs) profile obtained by mass spectrometry

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change from Baseline fecal microbiota profile by DNA 16S sequencing at 3 months
Time Frame: At 3 months from baseline
At 3 months from baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical response for Crohn Disease
Time Frame: At baseline (day 0) and at 3 months from baseline
Harvey-Bradshaw score
At baseline (day 0) and at 3 months from baseline
Clinical response for ulcerative colitis (UC)
Time Frame: At baseline (day 0) and at 3 months from baseline
Mayo score
At baseline (day 0) and at 3 months from baseline
Clinical response for spondyloarthritis (SpA)
Time Frame: At baseline (day 0) and at 3 months from baseline
BASDAI or Ankylosing Spondylarthritis Disease Activity Score (ASDAS) score
At baseline (day 0) and at 3 months from baseline
Ratio of circulating Th17 / Treg lymphocytes
Time Frame: At baseline (day 0) and at 3 months from baseline
At baseline (day 0) and at 3 months from baseline
Only for UC group : Analysis of endoscopic activity
Time Frame: At baseline (day 0) and at 3 months from baseline
Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score
At baseline (day 0) and at 3 months from baseline
Only for UC group : Analysis of histological activity
Time Frame: At baseline (day 0) and at 3 months from baseline
Riley score
At baseline (day 0) and at 3 months from baseline
Change from Baseline Volatile Organic Compounds (VOCs) profile at 3 months
Time Frame: At baseline (day 0) and at 3 months from baseline
VOCs levels will be obtained from exhaled air samples analyzed by mass spectrometry
At baseline (day 0) and at 3 months from baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bordeaux

Investigators

  • Study Director: Thomas BAZIN, MD, Assistance Publique - Hôpitaux de Paris
  • Study Chair: Rodolphe THIEBAUT, Prof, CHU Bordeaux
  • Principal Investigator: Pauline RIVIERE, MD, CHU Bordeaux

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 5, 2018

Primary Completion (Actual)

September 16, 2021

Study Completion (Actual)

September 16, 2021

Study Registration Dates

First Submitted

November 10, 2017

First Submitted That Met QC Criteria

November 30, 2017

First Posted (Actual)

December 2, 2017

Study Record Updates

Last Update Posted (Actual)

May 26, 2022

Last Update Submitted That Met QC Criteria

May 25, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2017/28

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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