Oral Fecal Microbiota Transplantation in Pediatric Ulcerative Colitis (T-FORE)

Assistance Publique - Hôpitaux de Paris

Status and phase: Not yet enrolling; Phase 2

Conditions: Pediatric Ulcerative Colitis in Remission

Treatments: Drug: Fecal Microbiota Transplantation by Intra-rectal enemas; Drug: Fecal Microbiota Transplantation by Stool capsules

Study type: Interventional

Funder types: Other

Identifiers

NCT05202990

APHP180572

2024-518044-20-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

The purpose of this study is to evaluate whether FMT by frozen stool capsules in pediatric UC patients in remission after corticosteroid treatment, can modify their dysbiotic gut microbiota by increasing the richness of their microbiota at 6 months.

Full description

Ulcerative colitis (UC) is characterized by chronic inflammation of the colon of undetermined origin. Their incidence is increasing dramatically in the paediatric population.

Pediatric-onset inflammatory bowel disease (IBD) is characterized by a greater severity than adult IBD. Although great progress has been made in recent years, the pathogenesis of IBD is not fully elucidated. During UC, an imbalance in the composition of gut microbiota, called "dysbiosis", has been identified. This dysbiosis is notably characterized by an increased proportion of pro-inflammatory microorganisms and a decreased proportion of anti-inflammatory microorganisms. The current treatments used in IBD mainly target the immune system through immunosuppressants, and help to shorten flairs and prevent recurrences, but there is no curative treatment.

From a therapeutic point of view, the correction of this dysbiosis is thus an attractive approach. Until now, efficacy of microbiome-based therapies such as probiotics or antibiotics has been disappointing in IBD. Fecal microbiota transplantation (FMT) consists of the administration of fecal material from a donor into the intestinal tract of a recipient to change their microbiota composition and restore healthy conditions. FMT has been successfully used for many years for the treatment of Clostridioides difficile infection. Recent studies seem to show a benefit of FMT in UC.

The investigator's main hypothesis is that the replacement of a dysbiotic microbiota by a 'healthy' microbiota by FMT can modify the richness of UC patient's microbiota and has a positive impact on the disease course.

Once steroid-induced remission will be achieved, patients will be included and randomised to receive either FMT by frozen stool capsules or enemas. They will receive 3 doses at 0, 1 and 2 months. They will be followed for one year with stool samples collected every 3 months. Clinical and laboratory data will be collected.

Enrollment: 26 estimated patients

Sex: All

Ages: 8 to 17 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for patients:

• Patient aged 8 to 17 years old

• Ulcerative colitis (UC), whatever the extent, except isolated proctitis (<5 cm), diagnosed for more than 3 months according to the usual clinical, biological and endoscopic criteria

• Moderate active UC defined by a PUCAI score > 35 and responding to corticosteroid treatment with a PUCAI score <10 at enrollment

• Treatment of UC (5-ASA, immunosuppressants, biotherapies) stable for more than 3 months

• Patient able to swallow test capsules

• For girls of childbearing age:

  • To have a negative blood (or urine) pregnancy test
  • To agree to use a reliable contraceptive method from visit 1 until the end of the research

• Patient with health insurance

• Informed written consent form signed by both parents or by the person (s) with parental authority

Exclusion Criteria for patients:

• isolated proctitis (<5 cm)
• Being on enteral nutrition
• Have received antibiotic or antifungal treatment in the 4 weeks prior to enrollment
• Having a Clostridioides difficile infection in the 4 weeks prior to enrollment;
• Being pregnant or breastfeeding, or have a positive pregnancy test;
• Have a contraindication to colonoscopy or general anaesthesia

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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26 participants in 2 patient groups

Fecal Microbiota Transplantation by Stool capsules

Experimental group

Description:

Patients receiving fecal microbiota transplantation from a healthy donor in 3 times after inclusion and randomisation (Month 0 - Month 1 - Month 2) using frozen stool capsules

Treatment:

Drug: Fecal Microbiota Transplantation by Stool capsules

Fecal Microbiota Transplantation by enema

Experimental group

Description:

Patients receiving fecal microbiota transplantation from a healthy donor in 3 times after inclusion and randomisation (Month 0 - Month 1 - Month 2) using frozen stool enemas.

Treatment:

Drug: Fecal Microbiota Transplantation by Intra-rectal enemas