RUMINOSPA: The Role of Intestinal Microbiota Dysbiosis in the Development of Spondyloarthritis

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Recruiting

CT.gov ID

NCT04853212

Collaborator

(none)

100

Enrollment

Location

Arms

24.5

Anticipated Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this case-control study aims to explore the role of bacterium Ruminococcus gnavus (R. gnavus) with intestinal biopsy and faecal sampling in the initiation and the development of spondyloarthritis (SPA) in comparison with health control subjets (patients without chronic disease but have indication to digestive endoscopy).

Condition or Disease	Intervention/Treatment	Phase
Spondyloarthritis Ruminococcus Gnavus	Procedure: Biopsy	N/A

Detailed Description

As secondary objectives, the study aims:

to research the abundance of bacterial strain of R. gnavus in mucosal sampling by biopsy;
to study the interaction between R. gnavus bacterium and mucus from histological sampling;
to correlate the expression of genes of intestinal mucus with the variations of identified microbiota of mucus biopsy;
to study the interaction between bacteria and intestinal epithelial cells during culture;
to demonstrate perturbations of the immune responses by dysbiosis.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

The Role of Dysbiosis of Intestinal Microbiota in the Development of Spondyloarthritis

Actual Study Start Date :

Jun 14, 2021

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: SPA patient Patients with SPA	Procedure: Biopsy Biopsy during recto-coloscopy
Sham Comparator: Subject without SPA Health subjects without SPA, planned to undergo a digestive endoscopy.	Procedure: Biopsy Biopsy during recto-coloscopy

Arm

Intervention/Treatment

Active Comparator: SPA patient

Patients with SPA

Procedure: Biopsy

Biopsy during recto-coloscopy

Sham Comparator: Subject without SPA

Health subjects without SPA, planned to undergo a digestive endoscopy.

Procedure: Biopsy

Biopsy during recto-coloscopy

Outcome Measures

Primary Outcome Measures

Isolation and characterization of R. gnavus [At the end of study, up to 2 years]
Isolation and characterization of R. gnavus bacterium from intestinal biopsy.
Bacteria analysis [At the end of study, up to 2 years]
Analysis of repartition of R. gnavus bacterium in each group and the comparison between 2 groups.

Secondary Outcome Measures

Bacterial strain's abundance [At the end of study, up to 2 years]
Compare the abundance by RT-q-PCR of bacterial strain (R. gnavus) between mucus biopsy sampling and faecal sampling, collected from PCR patients or control subjects respectively.
Mucin-degradation of Ruminococcus gnavus [At the end of study, up to 2 years]
Study the ability of the strain to grow on mucins of intestinal biopsy, colored after fixation to carnoy.
RNA sequencing analysis of biopsy [At the end of study, up to 2 years]
RNA sequencing analysis of rectal biopsy between SPA patients and control subjects.
Interaction between bacteria and intestinal epithelial cells [At the end of study, up to 2 years]
In order to study the interaction between bacteria and intestinal epithelial cells in culture (organoids). Study the induction of several target genes as peptides anti-microbians, mucin or chemokines by RT-q-PCR.
Dysbiosis-induced immune perturbations [At the end of study, up to 2 years]
To compare between 2 groups their reactivities of T cells from intestinal biopsy which contact with cells of exposed antigens in vitro, to R. gnavus stains or to other stains biopsied from control subjects.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Patients with SPA:

Patients ⩾ 18 years;
Diagnosed as spondyloarthritis (SpA) according ASAS classification;
Affiliated to a social security scheme;
Have signed the written informed consent form.

Control subjects:

Subjects ⩾ 18 years;
Subjects free of SPA and planned for a digestive endoscopy for another indication such as to explore the risk of colorectal cancer in family member;
Affiliated to a social security scheme;
Have signed the written informed consent form.

Exclusion Criteria:

Subjects unable to understand the proposed study and/or sign a informed consent form;
Pregnant women or breast feeding women;
Subjects under guardianship or curatorship;
Have taken antibiotic 1 month prior to inclusion;
Presenting acute or chronic severe pathology may likely to interfere with the interpret of outcome;
Refusal of subjects to participate to the study;
Foreign patients under french AME scheme.