Fecal Microbiota Transplantation in Pediatric Ulcerative Colitis (UC)

Study Overview
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Brief Summary
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This study included two topics: one was to test the efficacy and safety of fecal microbiota transplants plus partial enteral nutrition (PEN) in refractory pediatric UC where conventional therapy has failed, and the other was to explore the efficacy and safety of FMT plus PEN as first-line therapy for pediatric active UC

Detailed Description
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Recent studies have suggested that gut imbalance and deregulation of immunological responses plays a pivotal role in the disease development of UC, and that FMT could be a useful treatment. In the refractory ulcerative colitis group, our study is aims to explore FMT plus PEN in the treatment of refractory pediatric UC. In the induction stage of UC, standard therapy remained unchanged, FMT and PEN treatment are added, and the investigators hope the withdrawal of conventional drug therapy was gradually reduced. Refractory UC is defined as refractory to standard therapy (e.g., steroids, immunomodulators, cyclosporine, tacrolimus, or anti-TNF agents). As a first-line treatment group for UC, our study is aims to explore FMT plus PEN as a first-line treatment for active UC in children. participants treated with FMT coupled with PEN are defined as the FMT group, and those treated with PEN coupled with mesalazine served as the PEN group. FMT treatment is given for at least one course of FMT treatment. If repeated FMTs are received, it is usually at a 2 month interval. All the participants received PEN (80% of total calories as a polymeric diet, Peptamen, Nestle, Vevey, and Switzerland) intervention to help induce and maintain clinical remission.

Official Title
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Repeated and Multiple Fecal Microbiota Transplantations in Active Pediatric Ulcerative Colitis (UC)

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Other: Fecal Microbiota Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age of older than 2 years and younger than 16 years with no genetic diseases; as a first-line treatment group for UC, newly diagnosed with mild-to-moderate UC (defined by the PUCAI of >10 and≤64); In the refractory ulcerative colitis group, all refractory pediatric with mild-to-moderate UC (defined by the PUCAI of >10 and≤64) defined by children who failed conventional treatment (hormone, immunosuppressant, biologics); agree to received regularly colonoscopy Exclusion Criteria: Children who were treated by PEN (80%) less than 8 weeks; As a first-line treatment group for UC, patients who were treated with corticosteroids, methotrexate, thiopurines, and anti-TNF agents as their first-line treatment; Known contraindication to all FMT infusion method such as nasoduodenal tube insertion, oesophago-gastro-duodenoscopy (OGD), enteroscopy, colonoscopy, enema and Fecal capsule; Unwilling to give informed consent/ assent

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FMT group<br>In the refractory ulcerative colitis group, our study is aims to explore repeated and multiple FMTs plus PEN in the treatment of refractory pediatric UC; | Other: Fecal Microbiota Transplantation<br>* In the induction stage of UC, FMT group received FMT and PEN intervention, and FMT group are given for at least one course of FMT treatment. If repeated FMTs are received, it is usually at a 2 month interval. All the participants received PEN (80% of total calories as a polymeric diet, Peptamen, Nestle, Vevey, and Switzerland) intervention to help induce and maintain clinical remission.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical response | reduction in the Pediatric Ulcerative Colitis Activity Index (PUCAI) ≥30% from baseline | 8-12 weeks after FMT | 
| clinical remission | Clinical remission defined as a PUCAI <10 | 8-12 weeks after FMT | 
| safety of FMT | All possible adverse events: fever, abdominal pain, infectious diseases and others. | 8-12 weeks after FMT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients requiring escalation of medical therapies | Number of patients requiring escalation of medical therapies based on clinical relapse. Clinical relapse is defined by requiring additional medical therapy. | 8-12 weeks after FMT | 
| Number of patients with endoscopic remission | Number of patients with endoscopic remission as defined by a PUCAI score of 0 | 8-12 weeks after FMT | 
| Fecal calprotectin level | Mean change of Fecal calprotectin levels | 8-12 weeks after FMT | 
| C-reactive protein levels | Mean change of C-reactive protein levels | 8-12 weeks after FMT | 
| erythrocyte sedimentation rate (ESR) level | Mean change of erythrocyte sedimentation rate (ESR) | 8-12 weeks after FMT | 
| The number of stools or bloody stools | Improvement in the number of stools or bloody stools | 8-12 weeks after FMT | 
| gut microbial | Fecal 16S RNA or macrogene sequencing was performed. Fecal samples were obtained from donor and recipient. The fecal samples and isolated microbiota samples were frozen immediately and underwent DNA extraction using standard methods. | before treatment and 4 weeks after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fecal microbiota transplantation, Ulcerative Colitis