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

Not Applicable

Completed

• Conditions: Spondyloarthritis; Crohn Disease; Ulcerative Colitis
• Interventions: Other: blood sample; Other: stool samples; Other: food questionnaire; Other: colonoscopy; Other: VOCs profile

• Registration Number: NCT03359642
• Lead Sponsor: University Hospital, Bordeaux

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.

Study Timeline

• Study First Submitted: 2017-11-10
• Study First Submitted QC: 2017-11-30
• Study First Posted: 2017-12-02
• Study Start: 2018-06-05
• Primary Completion: 2021-09-16
• Study Completion: 2021-09-16
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-25
• Last Update Posted: 2022-05-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients with anti-TNF alpha	blood sample	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.
Patients with anti-TNF alpha	colonoscopy	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.
Patients with anti-TNF alpha	VOCs profile	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.
Patients with anti-TNF alpha	stool samples	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.
mirror group	stool samples	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.
Patients with anti-TNF alpha	food questionnaire	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.
mirror group	food questionnaire	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.
mirror group	blood sample	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.
mirror group	VOCs profile	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.
mirror group	colonoscopy	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.

Primary Outcome Measures

Name	Time	Method
Change from Baseline fecal microbiota profile by DNA 16S sequencing at 3 months	At 3 months from baseline

Secondary Outcome Measures

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

Trial Locations

Locations (1)

CHU de Bordeaux - service d'Hépato-gastroentérologie; 🇫🇷 Pessac, France