Biomedicines and Bacterial Translocation in Spondyloarthritis (TEARE-BIO)

Bacterial Translocation in Spondyloarthritis: Evaluation Before and After Starting a Biomedicine.

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.

Study Overview

• Status: Recruiting
• Conditions: Axial Spondyloarthritis
• Intervention / Treatment: Other: Blood sample; Drug: anti-TNF antibody administration; Drug: anti-IL-17 antibody administration

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.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Frank Verhoeven, MD; Phone Number: +33381668241; Email: fverhoeven@chu-besancon.fr

Study Locations

• France
  • Besançon, France, 25000
    • Recruiting
    • CENTRE HOSPITALIER UNIVERSITAIRE de BESANCON
    • Contact: Frank Verhoeven, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NSAIDs; Patients responding to any class of NSAIDs and unlikely to initiate biotherapy	Other: Blood sample; Blood samples (2 times; 21mL per visit)
Experimental: Anti-TNF antibody; Patients requiring the introduction of biotherapy according to current recommendations and randomized to the anti-TNF treatment arm	Other: Blood sample; Blood samples (2 times; 21mL per visit); Drug: anti-TNF antibody administration; Anti-TNF antibody administration, according to current recommendations and randomization results
Experimental: Anti-IL17 antibody; Patients requiring the introduction of biotherapy according to current recommendations and randomized to the anti-IL-17 treatment arm	Other: Blood sample; Blood samples (2 times; 21mL per visit); Drug: anti-IL-17 antibody administration; Anti-IL-17 antibody administration, according to current recommendations and randomization results

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in serum LPS concentration	Difference in serum LPS concentration, measured by liquid chromatography-mass spectrometry, between D0 (before anti-TNF or anti-IL 17) and D90	3 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2022
• Primary Completion (Anticipated): February 1, 2025
• Study Completion (Anticipated): May 1, 2025

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: February 7, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 31, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: bacterial translocation
• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Bone Diseases, Infectious; Spondylitis; Spondylarthritis; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins
• Other Study ID Numbers: 2021/577

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No