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

Ulcerative Colitis Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03359642
• Other study ID #: CHUBX 2017/28
• Status: Completed
• Phase: N/A
• Start date: June 5, 2018
• Est. completion date: September 16, 2021

Study information

• Verified date: May 2022
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: September 16, 2021
• Est. primary completion date: September 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease
• Inflammatory Bowel Diseases
• Intestinal Diseases
• Spondylarthritis
• Spondyloarthritis
• Ulcerative Colitis

Intervention

Other:
• blood sample
14 ml whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation
• stool samples
Study of the fecal microbiota
• food questionnaire
food questionnaire on the seven days before the collection
• colonoscopy
Only for patients with ulcerative colitis (in routine care)
• VOCs profile
Volatile Organic Compounds (VOCs) profile obtained by mass spectrometry

Locations

Country	Name	City	State
France	CHU de Bordeaux - service d'Hépato-gastroentérologie	Pessac

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline fecal microbiota profile by DNA 16S sequencing at 3 months		At 3 months from baseline
Secondary	Clinical response for Crohn Disease	Harvey-Bradshaw score	At baseline (day 0) and at 3 months from baseline
Secondary	Clinical response for ulcerative colitis (UC)	Mayo score	At baseline (day 0) and at 3 months from baseline
Secondary	Clinical response for spondyloarthritis (SpA)	BASDAI or Ankylosing Spondylarthritis Disease Activity Score (ASDAS) score	At baseline (day 0) and at 3 months from baseline
Secondary	Ratio of circulating Th17 / Treg lymphocytes		At baseline (day 0) and at 3 months from baseline
Secondary	Only for UC group : Analysis of endoscopic activity	Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score	At baseline (day 0) and at 3 months from baseline
Secondary	Only for UC group : Analysis of histological activity	Riley score	At baseline (day 0) and at 3 months from baseline
Secondary	Change from Baseline Volatile Organic Compounds (VOCs) profile at 3 months	VOCs levels will be obtained from exhaled air samples analyzed by mass spectrometry	At baseline (day 0) and at 3 months from baseline