The Effect of Therapeutic Fecal Transplant on the Gut Microbiome in Children With Ulcerative Colitis

Study Overview
=================
Brief Summary
-----------------
Ninety Six patients with mild to moderate ulcerative colitis will be randomized to double blind, placebo controlled study. The safety and efficacy of the intervention will be closely monitored.

Detailed Description
-----------------
The enteric microbiota is now accepted as an important etiologic factor in the pathogenesis of human Inflammatory Bowel Disease (IBD) and immune-mediated chronic experimental intestinal inflammation, with ample data to implicate the microbiome as a main factor in the occurrence of IBD. This can be inferred from animals in germ-free environment which can protect from experimental colitis. In addition, increased gut permeability due to dysbiosis, is frequently seen in patients with IBD even in remission and, similarly, first degree relatives of IBD. Therefore, it is not surprising that therapeutic interventions aiming at modifying the gut microbiome would be of therapeutic benefit. Ulcerative colitis is a condition that is characterized by chronic inflammation of the colon. It is an important pediatric disease as 25% of all cases begin in childhood and its incidence is continuously on the rise. It is believed to be related to a genetically and environmentally-generated altered immune response to the enteric microbiome. Previous work in the PI's laboratory suggests that children harbor a unique gut microbial profile, which can predict therapeutic response. Therefore, modifying the gut microbiome may result in therapeutic benefit. However, attempts to modify the gut microbiome were largely unsuccessful until the advent of fecal transplant, which is a new approach in treating colitis. Fecal microbiota transplant (FMT) has been introduced several decades ago in an attempt to restore the gut microbial balance and it appears to be a more efficient method to effectively change and sustain the gut microbial composition. To date there have been a number of successful reports to suggest control of disease activity and in some cases cure of the disease. This study aims to further determine the safety and efficacy of FMT in treating children with ulcerative colitis

Official Title
-----------------
The Effect of Therapeutic Fecal Transplant on the Gut Microbiome in Children With Ulcerative Colitis

Conditions
-----------------
Ulcerative Colitis

Intervention / Treatment
-----------------
* Biological: Fecal Microbial Transplant


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Age: 7-21 who have been diagnosed with ulcerative colitis Mild to moderate disease based on PUCAI with a score of 10-64 Need for colonoscopy Exclusion Criteria Children who are known to be resistant to steroid therapy, immunomodulators and biologics, or on a steroid dose greater than 0.5 mg/kg/day (maximum 20 mg) Children with recent dose change of biologics (within 4 weeks), 5-ASA, steroids or immunomodulators (within 4 weeks) Allergy to or intolerance of mesalamine or 5-ASA products Any evidence of infectious colitis Concurrent infections that require anti-microbial therapy (such as abdominal abscess, pneumonia, etc…) Unable to give informed consent/assent Have received probiotic preparations ≤ 4 weeks prior to randomization Pregnancy and breast feeding in patient subjects of childbearing potential Subjects with significant renal and liver dysfunction (creatinine > 2 mg/dl and direct bilirubin > 2 mg/dl), Subjects with congenital or acquired immunodeficiency, or who are immunosuppressed due to conditions other than ulcerative colitis (such as neoplastic disease or organ transplantation), have received or are receiving chemotherapy, or have been diagnosed with HIV.

Ages Eligible for Study
-----------------
Minimum Age: 7 Years
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Patient Stool Transplant<br>Arm 1 will get FMT (Fecal Microbial Transplant) placebo and high dose 5-ASA (Pentasa). The FMT is done through colonoscopy. | Biological: Fecal Microbial Transplant<br>* Fecal Transplant via Colonoscopy.<br>* Other names: FMT;|
| Active Comparator: Donor Stool Transplant<br>Arm 2 will get FMT (Fecal Microbial Transplant) with Healthy Donor Stool and high dose 5-ASA (Pentasa). The FMT is done through colonoscopy. | Biological: Fecal Microbial Transplant<br>* Fecal Transplant via Colonoscopy.<br>* Other names: FMT;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is disease remission based on PUCAI scores (<10). | The primary outcome including results of disease activity, and safety measures. | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary endpoints will include change in mucosal inflammation reflected on laboratory studies. | Secondary endpoints include changes in gut microbial diversity - determined by gut microbial genomics and proteomics, and outcome measures for mucosal inflammation and repair including laboratory testing such as the level for C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as well as the stool calprotectin level. | 12 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fecal transplant