Capsulized Fecal Microbiota Transplantation in Pediatric Ulcerative Colitis Patients

Study Overview
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Brief Summary
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Fecal Microbiota Transplantation(FMT) - reconstitution of normal flora by a stool transplant from a healthy individual, is increasingly being recognized as a therapeutic modality for diseases that are associated with gut dysbiosis. This is a placebo-controlled, double blinded interventional study evaluating multiple, oral, fecal microbiota transplantation, administered in newly diagnosed pediatric patients with mild-moderate UC. The primary objective is to assess the safety and feasibility of multiple, oral, fecal microbiota transplantation, in newly diagnosed pediatric patients with mild-moderate UC. All processing will occur at the Center for Microbiome Research at Assaf Harofeh Medical Center, under GMP conditions.

Official Title
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High Intensity, Multi-Donor, Oral Capsulized Fecal Microbiota Transplantation in Newly Diagnosed Pediatric Patients With Mild to Moderate Ulcerative Colitis - a Double Blind, Placebo-Controlled Trial

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Other: Fecal transplantation
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients newly diagnosed (>9 months) with mild to moderate ulcerative colitis as per colonic biopsy and clinical disease activity (SCCAI 5-12). Patients not started on immune-suppressive or anti-inflammatory medications (Mesalamine is allowed). Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women of childbearing potential will have a urine pregnancy test, which must be negative, on Study Day 1, prior to receiving FMT. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for 3 months after FMT. Ability to understand and the willingness to sign a written document, including the willingness to accept risk of unrelated donor stool. Ability of parents or other legal guardian to understand and the willingness to sign a written informed consent document, including the willingness to accept risk of unrelated donor stool. Ability to swallow oral medications. Exclusion Criteria: Severe, uncontrolled ulcerative colitis. At time of enrollment, immune-suppressive or anti-inflammatory medications, except Mesalamine. Patients with active or uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy. Delayed gastric emptying syndrome Known chronic aspiration Patients with a history of significant allergy to foods not excluded from the donor diet (excluded foods are tree nuts, peanuts, shellfish, eggs) Pregnant and breast-feeding women Participants who are unable to swallow pills.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a placebo-controlled, double blinded interventional study evaluating oral, fecal microbiota transplantation, administered in patients with mild-moderate UC.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fecal transplantation<br>Fecal transplantation of feces from healthy donor via capsules. Oral application. | Other: Fecal transplantation<br>* Fecal transplantation administered orally via frozen capsules.<br>|
| Placebo Comparator: Placebo<br>Placebo capsules | Other: Placebo<br>* Placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UC remission | UC remission at week 12 defined as a Simple Clinical Colitis Activity Index<3 | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in UC symptoms | defined as improvement in SCCAI | 12 weeks | 
| markers of inflammation | Laboratory markers of inflammation - CRP, WBC, ANC, stool calprotectin | 12 weeks, 6 months and 12 months | 
| Improvement in UC endoscopic score | Mayo-score | 12 weeks, 6 months and 12 months | 
| change in gut microbiome | Diversity and variability of gut microbiome | 12 weeks, 6 and 12 months. | 
| use of treatments for UC | such as glucocorticoids, immunosuppressive therapy (eg, azathioprine), or tumor necrosis factor antagonists. | 6+12 months | 
| Extra-intestinal disease manifestations | Extra-intestinal disease manifestations | 6 and 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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UC, IBD, fecal-transplantation, capsules, microbiota, microbiome, colitis, pediatric