Fecal Microbiota Transplantation in Crohn's Disease as Relay After Anti-TNF Withdrawal
NCT ID: NCT04997733
Last Updated: 2025-08-11
Study Results
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Basic Information
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RECRUITING
PHASE3
150 participants
INTERVENTIONAL
2021-09-22
2029-07-22
Brief Summary
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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.
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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Fecal microbiota
Patients receiving the fecal microbiota transplantation (FMT) in 3 times after inclusion and randomisation (endoscopic and oral)
Fecal Microbiota Transplantation (FMT)
The colonoscopy for FMT will be planned between 7 and 14 days after the last adalimumab or sub-cutaneous infliximab administration and 6 weeks +/- 7 days after the last intravenous infliximab administration 14 and 28 days following the last sub-cutaneous golimumab administration. After colon cleansing using polyethylene glycol, the patient will have a colonoscopy under general anesthesia. The patient will then receive either FMT (frozen preparation of 50g of stools in 300ml of saline (NaCl 0.9%), (FMT vehicle in the terminal ileum or the colon.
At W12 and W24 after first colonoscopy, the patient receives treatment by capsule (15 capsules contain 0.8g of stools by visit).
Sham-transplantation
Patients receiving the sham-transplantation in 3 times after inclusion and randomisation (endoscopic and oral)
Sham-transplantation (placebo)
The colonoscopy for sham-transplantation will be planned between 7 and 14 days after the last adalimumab or sub-cutaneous infliximab administration and 6 weeks +/- 7 days after the last intravenous infliximab administration, 14 and 28 days following the last sub-cutaneous golimumab administration. After colon cleansing using polyethylene glycol, the patient will have a colonoscopy under general anesthesia. The patient will then receive either sham transplantation (frozen preparation of NaCl 0.9% with 10% glycerol) in the terminal ileum or the colon.
At S12 and S24 after first colonoscopy, the patient receives treatment by capsule (15 capsules contain placebo).
Interventions
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Fecal Microbiota Transplantation (FMT)
The colonoscopy for FMT will be planned between 7 and 14 days after the last adalimumab or sub-cutaneous infliximab administration and 6 weeks +/- 7 days after the last intravenous infliximab administration 14 and 28 days following the last sub-cutaneous golimumab administration. After colon cleansing using polyethylene glycol, the patient will have a colonoscopy under general anesthesia. The patient will then receive either FMT (frozen preparation of 50g of stools in 300ml of saline (NaCl 0.9%), (FMT vehicle in the terminal ileum or the colon.
At W12 and W24 after first colonoscopy, the patient receives treatment by capsule (15 capsules contain 0.8g of stools by visit).
Sham-transplantation (placebo)
The colonoscopy for sham-transplantation will be planned between 7 and 14 days after the last adalimumab or sub-cutaneous infliximab administration and 6 weeks +/- 7 days after the last intravenous infliximab administration, 14 and 28 days following the last sub-cutaneous golimumab administration. After colon cleansing using polyethylene glycol, the patient will have a colonoscopy under general anesthesia. The patient will then receive either sham transplantation (frozen preparation of NaCl 0.9% with 10% glycerol) in the terminal ileum or the colon.
At S12 and S24 after first colonoscopy, the patient receives treatment by capsule (15 capsules contain placebo).
Eligibility Criteria
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Inclusion Criteria
* Crohn's disease (according to the Lennard-Jones criteria) for at least 6 months
* Patient in steroid-free clinical remission for at least 6 months under anti-TNF agent (no clinical evidence of flare nor change in Crohn's disease specific treatment (anti-TNF, immunosuppressive, …) within 6 months before inclusion) and CDAI \<150 the week before inclusion) and willing to withdraw anti-TNF treatment
* Female of child-bearing age with an active contraception and this during at least the period of treatment (week 52)
* Patient with health insurance
* Informed Written consent
* Age ≥ 18 years and \< 50 years
* 17 kg/m² \< body mass index \< 30 kg/m²
* Regular bowel movement defined as at least 1 stool every other day and maximum 2 stools per day
* Subject with health insurance (AME excepted)
* Informed written consent
Exclusion Criteria
* Contraindication to colonoscopy or anesthesia
* Pregnancy or breastfeeding during the study (Cf. Addendum 4)
* Diagnosis of Crohn's disease restricted to the upper gastrointestinal tract (oesophagus, stomach, duodenum, jejunum)
* Patient with active perineal disease (defined as evidence of perineal abscess or active draining fistula or presence of seton or presence of perineal ulceration)
* History of more than one small bowel resection or small intestine resection \> 1 meter
* Current stoma (Ileostomy or a colostomy) or stoma in the last 6 months or any other intra-abdominal surgery within 3 months prior to inclusion
* Participation in any other interventional study
* Patient under legal protection
\- For details, please see protocol
18 Years
74 Years
ALL
Yes
Sponsors
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CRB-HUEP
UNKNOWN
Institut National de la Santé Et de la Recherche Médicale, France
OTHER_GOV
Assistance Publique - Hôpitaux de Paris
OTHER
Responsible Party
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Principal Investigators
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Harry SOKOL, PU-PH
Role: PRINCIPAL_INVESTIGATOR
Assistance Publique - Hôpitaux de Paris
Locations
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Gastroenterology Department of Saint Antoine Hospital
Paris, , France
Countries
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Central Contacts
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Facility Contacts
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References
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Related Links
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Other Identifiers
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2019-003816-29
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
APHP190183
Identifier Type: -
Identifier Source: org_study_id
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