Fecal Microbiota Transplantation (FMT) in the Management of Ulcerative Colitis (UC)

Study Overview
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Brief Summary
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Inflammatory bowel disease is a condition caused by gastrointestinal immune system dysregulation and affected by both genetic and environmental factors. Differences in intestinal bacteria exist between IBD patients and healthy controls, but the role of intestinal bacteria in the development and treatment of IBD remains largely unknown. Fecal microbiota transplantation (FMT) is the transfer of gastrointestinal bacteria from a healthy donor to a patient with altered microbial diversity with the intent of restoring a normal bacterial balance. Most studies focus on its use in treating Clostridium difficile (CDI), an infection characterized by dysbiosis. Given the role of dysbiosis in IBD, the investigators hypothesize that FMT may be beneficial in IBD. The purpose of this study is to prospectively examine the safety of FMT in the management of ulcerative colitis (UC).

Detailed Description
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Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) with significant morbidity and mortality. Current therapies remain limited by side effects and loss of response over time, and there is an ongoing need for new therapies. Fecal microbiota transplantation (FMT), which has proven to be safe and effective in the management of Clostridium difficile infection (CDI) has been proposed as a therapy for UC. There have been studies examining the role of FMT in UC, but they have shown mixed results, and have not examined the underlying immunologic and microbial changes to explain how and why FMT works from specific donors and in certain recipients. Furthermore, no studies have examined the long-term safety of FMT in patients with UC. This proposal aims to examine: (a) the short- and long-term safety of FMT in patients with UC, (b) the efficacy of FMT as a therapy for mild-moderate UC, and (c) the microbial and immunologic changes that occur after FMT, to help understand how and why it works in this group of patients.

Official Title
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Fecal Microbiota Transplantation (FMT) in the Management of Ulcerative Colitis (UC)

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Biological: Fecal Microbiota Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with biopsy proven ulcerative colitis (UC), including those with inadequately controlled UC (flare) as defined by failure of standard medical therapy, steroid-dependence, and/or need for escalation of medical care as determined by severity index (Mayo Score), endoscopic or histologic study, and/or medical provider Have active disease, defined with a Mayo Score > 3 and Mayo endoscopic subscore >1 Subjects whom the investigator believes can and will comply with the requirements of the protocol Able to provide informed written consent. Exclusion Criteria: Biopsy-proven Crohn's disease or indeterminate colitis Acute abdomen or other clinical emergencies requiring emergent management (for example: stricture, bowel obstruction, perforation and/or abscess) Primary sclerosing cholangitis (PSC) Pregnancy Concurrent Clostridium difficile infection or other known infection Prior history of fecal microbiota transplantation Other causes of diarrhea, including but not limited to tube feeds and medications (for example, kayaxelate, metformin, lactulose, laxatives, magnesium) Major congenital defects Subjects with recent malignancy in the last 5 years, excluding non-melanoma skin malignancies Anaphylactic reactions to any foods Any antibiotic use within the last 3 months Subject having any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the participant participating in the study, would make it unlikely for the participant to complete the study, or would confound the study

Ages Eligible for Study
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Minimum 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fecal Microbiota Transplantation<br>Individuals with Ulcerative Colitis will undergo a fecal microbiota transplantation. | Biological: Fecal Microbiota Transplantation<br>* We will use fecal microbiota transplantation (FMT), with fecal material obtained from OpenBiome or donor directed, to assess safety (as primary outcome) and efficacy (as secondary outcome) in adult (>18 year old) patients with active ulcerative colitis (UC).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety post-FMT as determined by interview for adverse events | Patient information regarding adverse events and safety of FMT for UC will be collected throughout the study period, including day 0, weeks 1, 2, 4, 6, 12 24, and then every 6 months until 36 months post-FMT. Throughout the study period, patients will be assessed for safety with questions regarding general well-being (such as how have you been feeling?), as well as specific questions to evaluate for occurrence of adverse events. Patients will also be questioned regarding stool form and frequency, presence of abdominal pain, fevers and subjective well-being. | 36 months post-FMT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical remission | Defined by Mayo score ≤ 2 without any subscore >1, and Mayo endoscopic subscore 0-1 | 2, 4 and 12 weeks post fecal microbiota transplantation | 
| Clinical Response | Defined by decrease in Mayo score by 3 points, decrease in bleeding subscore by 1, or absolute subscore of 0-1 | 2, 4 and 12 weeks post fecal microbiota transplantation | 
| Progression of disease defined by initiation of anti-TNF agents | Initiation of anti-TNF agents (such as infliximab, adalimumab, certolizumab), vedolizumab, steroids. Includes time gap until additional agents are started | 2, 4 and 12 weeks post fecal microbiota transplantation | 
| Progression of disease defined by increase in dosages of current UC medications | Increase in dosages of current ulcerative colitis specific medications | 2, 4 and 12 weeks post fecal microbiota transplantation | 
| Progression of disease defined by time to colectomy | Time to colectomy rates and increase in time to colectomy | up to three year follow-up period post fecal microbiota transplantation | 
| Death secondary to UC | Time to death secondary to ulcerative colitis | Anytime during the three year follow-up period post fecal microbiota transplantation | 
| Progression of disease defined by clinical flare | Time to next flare | 2, 4 and 12 weeks post fecal microbiota transplantation | 
| Microbial changes | - Alterations in microbial profiles as defined by sequence of genetic material from fecal material. | 0, 2 and 4 weeks post fecal microbiota transplantation | 
| Immunological changes | - Alterations in immune cell function as defined by RNA sequencing and flow cytometry | 0, 2 and 4 weeks post fecal microbiota transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fecal Microbiota Transplantation, Ulcerative Colitis