Pediatric Ulcerative Colitis in Remission
Conditions
Keywords
Ulcerative Colitis, Pediatric Onset Inflammatory Bowel Disease, Microbiota, Fecal Microbiota Transplantation, Stool capsule, Intra-rectal enemas
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.
Interventions
DRUGFecal Microbiota Transplantation by Stool capsules
After colon cleansing using PolyEthylen glycol, the patient will have a colonoscopy under general anaesthesia. The patient will then receive orally FMT (frozen stools capsules prepared from healthy donor feces).
DRUGFecal Microbiota Transplantation by Intra-rectal enemas
After colon cleansing using Polyethylen glycol, the patient will have a colonoscopy under general anaesthesia. The patient will then receive first FMT (frozen preparation of stools) by infusion in caecum during colonoscopy and the second and third doses by enemas.
Sponsors
Assistance Publique - Hôpitaux de Paris
MRSU 938 - Research Center of Saint Antoine
URC-CIC Paris Descartes Necker Cochin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Success of FMT with frozen stool capsules defined by an increase in the richness of the recipient's microbiota at 6 months. | 6 months after the first Fecal Microbiota Transplantation (FMT) | Success of FMT is defined by an increase in the richness of the recipient's microbiota at 6 months. Microbiota richness will be evaluated by measuring the alpha diversity of the microbiota using Shannon index. The success of the FMT will be defined by an increase in the Shannon index of 0.5 points between the recipient microbiota at M0 and the recipient microbiota at M6. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Success of FMT with frozen stool capsules defined by an increase in the richness of the recipient's microbiota at 12 months | 12 months after the first FMT | The success of the FMT will be defined by an increase in the Shannon index of 0.5 points between the recipient microbiota at M0 and the recipient microbiota at M12. |
| Success of FMT by stool enema defined by an increase in the richness of the recipient's microbiota at 6 and 12 months | 6 and 12 months after the first FMT | The success of the FMT will be defined by an increase in the Shannon index of 0.5 points between the recipient microbiota at M0 and the recipient microbiota at M6 and M12 |
| Success of FMT with frozen stool capsules on the change of recipient dysbiotic microbiota at 6 and 12 months | 6 and 12 months after the first FMT | The success of the FMT will be defined by a Bray Curtis (BC) Index \[recipient after FMT vs donnor\] greater than a BC Index \[recipient after FMT vs recipient before FMT\], with a BC Index \[recipient after FMT vs donnor\] ≥ 0.6. |
| Success of FMT by enema on the change of recipient dysbiotic microbiota at 6 and 12 months | 6 and 12 months after the first FMT | The success of the FMT will be defined by a Bray Curtis (BC) Index \[recipient after FMT vs donnor\] greater than a BC Index \[recipient after FMT vs recipient before FMT\], with a BC Index \[recipient after FMT vs donnor\] ≥ 0.6. |
| Success of FMT with frozen stool capsules on the richness and change of mucosal microbiota at 12 months | 12 months | The success of the FMT will be defined by an increase in the Shannon index of 0.5 points between the mucosal recipient microbiota at M0 and the mucosal recipient microbiota at M12 |
| Success of FMT by enema on the richness and change of mucosal microbiota at 12 months | 12 months | The success of the FMT will be defined by an increase in the Shannon index of 0.5 points between the mucosal recipient microbiota at M0 and the mucosal recipient microbiota at M12 |
| Success of FMT with frozen stool capsules on the change of mucosal recipient dysbiotic microbiota at 6 and 12 months | 6 and 12 months after the first FMT | The success of the FMT will be defined by a Bray Curtis (BC) Index \[recipient after FMT vs donnor\] greater than a BC Index \[recipient after FMT vs recipient before FMT\], with a BC Index \[recipient after FMT vs donnor\] ≥ 0.6. |
| Success of FMT by enema on the change of mucosal recipient dysbiotic microbiota at 6 and 12 months | 6 and 12 months after the first FMT | The success of the FMT will be defined by a Bray Curtis Index \[recipient after FMT vs donnor\] greater than a BC Index \[recipient after FMT vs recipient before FMT\], with a BC Index \[recipient after FMT vs donnor\] ≥ 0.6. |
| FMT with frozen stool capsules Feasibility | At inclusion, 1 and 2 months after each FMT | Number of capsules intake, facility of capsules intake, tolerance, intake duration |
| FMT by enema Feasibility | At inclusion, 1 and 2 months after each FMT | Number of enemas, tolerance , enemas duration, difficulties related to the application of enemas |
| Ulcerative colitis clinical relapse | 6 and 12 months | Defined as a Pediatric Ulcerative Colitis Activity Index (PUCAI) \> 35, number of relapses during the follow-up, treatments received during the follow-up |
| Ulcerative colitis Endoscopic relapse | 12 months | Defined as an Ulcerative Colitis Endoscopic Index of Severity (UCEIS) ≥ 2 |
| Change of inflammatory blood markers from baseline to 12 months | At inclusion, 6, 9 and 12 months | CRP, VS, Leucocytes levels |
| Change of faecal calprotectin from baseline to 12 months | At inclusion, 6, 9 and 12 months | Calprotectin level |
| Change of patient's quality of life evaluated with IMPACT-3 questionnaire from inclusion until 12 months | At inclusion 2, 6, 9 and 12 months | IMPACT-3 questionnaire of 35 closed questions - scale ranging from 1 to 5 for all answers - higher score suggesting better quality of life |
| Incidence of adverse events | 26 months | — |
Countries
France
Contacts
CONTACTBénédicte PIGNEUR, MD,PhD
CONTACTGael Plastow, PhD
PRINCIPAL_INVESTIGATORBénédicte PIGNEUR, MD, PhD
AP-HP - Department of Pediatric Gastroenterology Hepatology and Nutrition - Necker - Enfants Malades Hospital
STUDY_DIRECTORHarry SOKOL, MD, PhD
AP-HP, Department of Gastroenterology and Nutrition - Saint Antoine Hospital
Outcome results
None listed