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

Phase 1

Completed

• Conditions: Ulcerative Colitis
• Interventions: Biological: Fecal Microbiota Transplantation

• Registration Number: NCT02516384
• Lead Sponsor: Weill Medical College of Cornell University

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2015-07-29
• Study First Submitted QC: 2015-08-04
• Study First Posted: 2015-08-05
• Study Start: 2016-10-01
• Primary Completion: 2016-12-31
• Study Completion: 2017-01-31
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-20
• Last Update Posted: 2018-02-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fecal Microbiota Transplantation	Fecal Microbiota Transplantation	Individuals with Ulcerative Colitis will undergo a fecal microbiota transplantation.

Primary Outcome Measures

Name	Time	Method
Safety post-FMT as determined by interview for adverse events	36 months post-FMT	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Weill Cornell Medical College; 🇺🇸 New York, New York, United States