Fecal Microbiota Transplantation in Crohn's Disease as Relay After Anti-TNF Withdrawal

Phase 3

Recruiting

• Conditions: Crohn Disease
• Interventions: Drug: Fecal Microbiota Transplantation (FMT); Drug: Sham-transplantation (placebo)

• Registration Number: NCT04997733
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Crohn's disease (CD) is a chronic inflammatory bowel disease. CD pathogenesis remains poorly understood but involves an inappropriate immune response toward an unbalanced gut microbiota in predisposed hosts.

The purpose of this study is to evaluate de clinical efficacy of the fecal microbiota transplantation (FMT) as a maintenance treatment following anti-TNF agent withdrawal in CD's patient.

Detailed Description

Crohn's disease (CD) is a chronic inflammatory bowel disease affecting approximately 120000 patients in France, mostly at young age, and altering their quality of life.

Immunosuppressive treatments in CD are expensive and associated with potentially severe complications.

Alternative treatment strategies are thus required. This is particularly the case for CD patients in remission under anti-TNF agents for which no specific recommendation are available.

CD pathogenesis remains poorly understood but involves an inappropriate immune response toward an unbalanced gut microbiota in predisposed hosts.

Fecal microbiota transplantation (FMT) is currently recommended for treating recurrent Clostridium difficile infection. Although the pathogenesis involved in CD differs, FMT is a potential therapeutic strategy that could restore the appropriate host-microbiota crosstalk by transferring a healthy microbiota in a CD patient. However, as the gut microbiota is dramatically altered by intestinal inflammation, transferring a massive amount of microbes in an inflamed gut with epithelial barrier disruption might be a suboptimal strategy and could even have detrimental effects by allowing bacterial translocation.

Results of randomized controlled trial (RCT) in CD are lacking to date. We performed a pilot RCT (NCT02097797), evaluating the impact of a single FMT in 18 CD patients who achieved remission by corticosteroid treatment. A higher rate of steroid free clinical remission was observed in the FMT arm at 24 weeks (57.1% vs 33.3% in FMT and control arm respectively). CD Endoscopic Index of Severity was also improved at 6 weeks in FMT (median 8.5 vs 3.5 p=0.03) but not in sham group (median 2.4 vs 2.7 p=0.8). Moreover, the only 2 patients who early relapsed in the FMT group were those who did not show any engraftment of donor microbiota at week 6. These promising data, currently submitted for publication, suggest that using FMT as a maintenance treatment in CD can be effective. However, these promising findings need to be confirmed by a Phase III RCT.

Study Timeline

• Study First Submitted: 2021-07-05
• Study First Submitted QC: 2021-07-31
• Study First Posted: 2021-08-10
• Study Start: 2021-09-22
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-02
• Last Update Posted: 2023-10-04
• Primary Completion: 2025-05-22
• Study Completion: 2027-07-22

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fecal microbiota	Fecal Microbiota Transplantation (FMT)	Patients receiving the fecal microbiota transplantation (FMT) in 3 times after inclusion and randomisation (endoscopic and oral)
Sham-transplantation	Sham-transplantation (placebo)	Patients receiving the sham-transplantation in 3 times after inclusion and randomisation (endoscopic and oral)

Primary Outcome Measures

Name	Time	Method
Evaluate the clinical efficacy of FMT versus sham transplantation as a maintenance treatment following anti-TNF agent withdrawal in patients with Crohn's disease in steroid-free clinical remission for at least 6 months under anti-TNF agent	52 weeks after FMT or sham-transplantation	Clinical remission (defined by a Crohn's disease activity index (CDAI) \<150) at week 52 (V8) without any flare between week 0 (colonoscopy (V2)) and week 52 (V8). Flare is defined by a CDAI (Addendum 2) above 250 or between 150 points and 250 points with a 70-point increase from baseline over 2 consecutive weeks and the need

Secondary Outcome Measures

Name	Time	Method
Relapse free survival	52 weeks after FMT or sham-transplantation	Relapse free survival rate from week 0 (V2) to week 52 (V8)

Trial Locations

Locations (1)

Gastroenterology Department of Saint Antoine Hospital; 🇫🇷 Paris, France