Clinical trial NCT03359642: 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
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
Overall status: COMPLETED
Phase: NA
Conditions: Spondyloarthritis
Crohn Disease
Ulcerative Colitis
Keywords: Microbiota
inflammatory bowel disease
inflammation
anti-TNF alpha
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2017-12-02
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Change from Baseline fecal microbiota profile by DNA 16S sequencing at 3 months
timeFrame: At 3 months from baseline
Secondary outcomes:
measure: Clinical response for Crohn Disease
timeFrame: At baseline (day 0) and at 3 months from baseline
measure: Clinical response for ulcerative colitis (UC)
timeFrame: At baseline (day 0) and at 3 months from baseline
measure: Clinical response for spondyloarthritis (SpA)
timeFrame: At baseline (day 0) and at 3 months from baseline
measure: Ratio of circulating Th17 / Treg lymphocytes
timeFrame: At baseline (day 0) and at 3 months from baseline
measure: Only for UC group : Analysis of endoscopic activity
timeFrame: At baseline (day 0) and at 3 months from baseline
measure: Only for UC group : Analysis of histological activity
timeFrame: At baseline (day 0) and at 3 months from baseline
measure: Change from Baseline Volatile Organic Compounds (VOCs) profile at 3 months
timeFrame: At baseline (day 0) and at 3 months from baseline
Other outcomes:
Locations:
city: Pessac
country: France
facility: CHU de Bordeaux - service d'Hépato-gastroentérologie
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Thomas BAZIN, MD
role: STUDY_DIRECTOR
affiliation: University Hospital, Bordeaux
name: Rodolphe THIEBAUT, Prof
role: STUDY_CHAIR
affiliation: University Hospital, Bordeaux
name: Pauline RIVIERE, MD
role: PRINCIPAL_INVESTIGATOR
References: