Clinical trial NCT05202990: Oral Fecal Microbiota Transplantation in Pediatric Ulcerative Colitis
Official title: Pilot Study of a New Technique of Oral Fecal Transplantation Using Frozen Stool Capsules for the Maintenance Treatment of Pediatric Ulcerative Colitis.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Pediatric Ulcerative Colitis in Remission
Keywords: Ulcerative Colitis
Pediatric Onset Inflammatory Bowel Disease
Microbiota
Fecal Microbiota Transplantation
Stool capsule
Intra-rectal enemas
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: MRSU 938 - Research Center of Saint Antoine
First posted: 2022-01-24
Enrollment: 26
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Success of FMT with frozen stool capsules defined by an increase in the richness of the recipient's microbiota at 6 months.
timeFrame: 6 months after the first Fecal Microbiota Transplantation (FMT)
Secondary outcomes:
measure: Success of FMT with frozen stool capsules defined by an increase in the richness of the recipient's microbiota at 12 months
timeFrame: 12 months after the first FMT
measure: Success of FMT by stool enema defined by an increase in the richness of the recipient's microbiota at 6 and 12 months
timeFrame: 6 and 12 months after the first FMT
measure: Success of FMT with frozen stool capsules on the change of recipient dysbiotic microbiota at 6 and 12 months
timeFrame: 6 and 12 months after the first FMT
measure: Success of FMT by enema on the change of recipient dysbiotic microbiota at 6 and 12 months
timeFrame: 6 and 12 months after the first FMT
measure: Success of FMT with frozen stool capsules on the richness and change of mucosal microbiota at 12 months
timeFrame: 12 months
measure: Success of FMT by enema on the richness and change of mucosal microbiota at 12 months
timeFrame: 12 months
measure: Success of FMT with frozen stool capsules on the change of mucosal recipient dysbiotic microbiota at 6 and 12 months
timeFrame: 6 and 12 months after the first FMT
measure: Success of FMT by enema on the change of mucosal recipient dysbiotic microbiota at 6 and 12 months
timeFrame: 6 and 12 months after the first FMT
measure: FMT with frozen stool capsules Feasibility
timeFrame: At inclusion, 1 and 2 months after each FMT
measure: FMT by enema Feasibility
timeFrame: At inclusion, 1 and 2 months after each FMT
measure: Ulcerative colitis clinical relapse
timeFrame: 6 and 12 months
measure: Ulcerative colitis Endoscopic relapse
timeFrame: 12 months
measure: Change of inflammatory blood markers from baseline to 12 months
timeFrame: At inclusion, 6, 9 and 12 months
measure: Change of faecal calprotectin from baseline to 12 months
timeFrame: At inclusion, 6, 9 and 12 months
measure: Change of patient's quality of life evaluated with IMPACT-3 questionnaire from inclusion until 12 months
timeFrame: At inclusion 2, 6, 9 and 12 months
measure: Incidence of adverse events
timeFrame: 26 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Department of gastroenterology, Armand Trousseau Hospital
city: Paris
country: France
facility: Department of Pediatric Gastroenterology, Hepatology and Nutrition - Necker - Enfants Malades Hospital
city: Paris
country: France
facility: Department of Pediatric Gastroenterology, Robert Debré Hospital
Study officials:
affiliation: AP-HP - Department of Pediatric Gastroenterology Hepatology and Nutrition - Necker - Enfants Malades Hospital
name: Bénédicte PIGNEUR, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: AP-HP, Department of Gastroenterology and Nutrition - Saint Antoine Hospital
name: Harry SOKOL, MD, PhD
role: STUDY_DIRECTOR
References: