Biomedicines and Bacterial Translocation in Spondyloarthritis

NCT ID: NCT05244109

Last Updated: 2022-06-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-07
• Study Completion Date: 2025-05-31

Brief Summary

The aim of this project is to evaluate the effect of anti-TNF and anti-IL17 biotherapies on bacterial translocation in patients with NSAID-resistant axial spondyloarthritis.

Detailed Description

Axial spondyloarthritis is a common inflammatory rheumatic disease and its management is based on the use of NSAIDs and biotherapies (anti-TNF and anti-IL17 antibodies). Its pathophysiology involves the digestive mucosa. The colon of patients with spondyloarthritis is the site of asymptomatic inflammation. This inflammation results from dysbiosis, which is responsible for activation of innate immunity linked to bacterial translocation phenomena. Dendritic cells are then activated and the immune response is polarized towards the IL23/Th17 axis. This translocation is secondary to an increase in colonic permeability. The increase in digestive permeability allows translocation of bacteria or bacterial fragments, primarily lipopolysaccharide (LPS).

Some proinflammatory cytokines (TNF, IFNγ, and IL23) cause an increase in digestive permeability. IL17 produced in the digestive mucosa has two different effects. Indeed, two types of colonic T cells produce IL17: regulatory T Helpers 17 producing IL10 and IL17 and inflammatory T Helpers 17 producing IL17 and IFNγ.

The investigators hypothesize that biotherapies decrease bacterial translocation. They suspect a lesser effect of anti-IL17 compared to anti-TNF because of the potential inhibition of Treg17 lymphocytes.

Conditions

Axial Spondyloarthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

NSAIDs

Patients responding to any class of NSAIDs and unlikely to initiate biotherapy

Group Type: EXPERIMENTAL

Blood sample

Intervention Type: OTHER

Blood samples (2 times; 21mL per visit)

Anti-TNF antibody

Patients requiring the introduction of biotherapy according to current recommendations and randomized to the anti-TNF treatment arm

Group Type: EXPERIMENTAL

Blood sample

Intervention Type: OTHER

Blood samples (2 times; 21mL per visit)

anti-TNF antibody administration

Intervention Type: DRUG

Anti-TNF antibody administration, according to current recommendations and randomization results

Anti-IL17 antibody

Patients requiring the introduction of biotherapy according to current recommendations and randomized to the anti-IL-17 treatment arm

Group Type: EXPERIMENTAL

Blood sample

Intervention Type: OTHER

Blood samples (2 times; 21mL per visit)

anti-IL-17 antibody administration

Intervention Type: DRUG

Anti-IL-17 antibody administration, according to current recommendations and randomization results

Interventions

Blood sample

Blood samples (2 times; 21mL per visit)

Intervention Type: OTHER

anti-TNF antibody administration

Anti-TNF antibody administration, according to current recommendations and randomization results

Intervention Type: DRUG

anti-IL-17 antibody administration

Anti-IL-17 antibody administration, according to current recommendations and randomization results

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Axial spondyloarthritis (2009 ASAS criteria)
• NSAID arm: Responding to any class of NSAID and not likely to initiate biotherapy
• anti-TNF/anti-IL-17 arms: Need to introduce a biomedical drug according to current recommendations (objective signs of inflammation, i.e. MRI sacroiliitis or increased CRP, and failure of two NSAIDs of different classes)

Exclusion Criteria

• IBD already diagnosed by a gastroenterologist or suspicion of IBD (bloody diarrhea)
• Previous exposure to a biomedical drug (anti TNF or anti IL 17).
• Antibiotic use in the 3 months prior to inclusion
• Contraindications for treatment with anti-TNF or anti-IL17 (for all patients)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Besancon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Centre Hospitalier Universitaire de Besançon

Besançon, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Frank Verhoeven, MD

Role: CONTACT

fverhoeven@chu-besancon.fr

+33381668241

Facility Contacts

Frank Verhoeven, MD

Role: primary

Other Identifiers

2021/577

Identifier Type: -

Identifier Source: org_study_id