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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)

Primary Purpose

Spondyloarthritis, Crohn Disease, Ulcerative Colitis

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
blood sample
stool samples
food questionnaire
colonoscopy
VOCs profile
Sponsored by
University Hospital, Bordeaux
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Spondyloarthritis focused on measuring Microbiota, inflammatory bowel disease, inflammation, anti-TNF alpha

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CHU de Bordeaux - service d'Hépato-gastroentérologie

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Patients with anti-TNF alpha

mirror group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Change from Baseline fecal microbiota profile by DNA 16S sequencing at 3 months

Secondary Outcome Measures

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

Full Information

First Posted
November 10, 2017
Last Updated
May 25, 2022
Sponsor
University Hospital, Bordeaux
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1. Study Identification

Unique Protocol Identification Number
NCT03359642
Brief Title
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
Acronym
MIST
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
June 5, 2018 (Actual)
Primary Completion Date
September 16, 2021 (Actual)
Study Completion Date
September 16, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Bordeaux

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spondyloarthritis, Crohn Disease, Ulcerative Colitis
Keywords
Microbiota, inflammatory bowel disease, inflammation, anti-TNF alpha

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Patients with anti-TNF alpha
Arm Type
Experimental
Arm Description
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.
Arm Title
mirror group
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
blood sample
Intervention Description
14 ml whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation
Intervention Type
Other
Intervention Name(s)
stool samples
Intervention Description
Study of the fecal microbiota
Intervention Type
Other
Intervention Name(s)
food questionnaire
Intervention Description
food questionnaire on the seven days before the collection
Intervention Type
Other
Intervention Name(s)
colonoscopy
Intervention Description
Only for patients with ulcerative colitis (in routine care)
Intervention Type
Other
Intervention Name(s)
VOCs profile
Intervention Description
Volatile Organic Compounds (VOCs) profile obtained by mass spectrometry
Primary Outcome Measure Information:
Title
Change from Baseline fecal microbiota profile by DNA 16S sequencing at 3 months
Time Frame
At 3 months from baseline
Secondary Outcome Measure Information:
Title
Clinical response for Crohn Disease
Description
Harvey-Bradshaw score
Time Frame
At baseline (day 0) and at 3 months from baseline
Title
Clinical response for ulcerative colitis (UC)
Description
Mayo score
Time Frame
At baseline (day 0) and at 3 months from baseline
Title
Clinical response for spondyloarthritis (SpA)
Description
BASDAI or Ankylosing Spondylarthritis Disease Activity Score (ASDAS) score
Time Frame
At baseline (day 0) and at 3 months from baseline
Title
Ratio of circulating Th17 / Treg lymphocytes
Time Frame
At baseline (day 0) and at 3 months from baseline
Title
Only for UC group : Analysis of endoscopic activity
Description
Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score
Time Frame
At baseline (day 0) and at 3 months from baseline
Title
Only for UC group : Analysis of histological activity
Description
Riley score
Time Frame
At baseline (day 0) and at 3 months from baseline
Title
Change from Baseline Volatile Organic Compounds (VOCs) profile at 3 months
Description
VOCs levels will be obtained from exhaled air samples analyzed by mass spectrometry
Time Frame
At baseline (day 0) and at 3 months from baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas BAZIN, MD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Rodolphe THIEBAUT, Prof
Organizational Affiliation
CHU Bordeaux
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Pauline RIVIERE, MD
Organizational Affiliation
CHU Bordeaux
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Bordeaux - service d'Hépato-gastroentérologie
City
Pessac
Country
France

12. IPD Sharing Statement

Learn more about this trial

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

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