Fecal Microbiota Transplantation for Ulcerative Colitis

Evaluation of Durability of Fecal Microbiota Transplantation in Patients With Mild to Moderate Ulcerative Colitis

Fecal microbiota therapy (FMT) is an emerging treatment for gastrointestinal disorders marked by an imbalance in the intestinal microbial flora (dysbiosis). It is hypothesized to work by shifting the recipient's microbiota toward a eubiotic microbial community that resists colonization by pathogenic organisms or decreases its inherent inflammatory properties. Several studies now report its efficacy in treatment of severe Clostridium difficile colitis. Preliminary studies using FMT in Ulcerative Colitis (UC) have also met with some success. This is corroborated by several lines of evidence suggesting dysbiosis plays an important role in UC pathogenesis. While a recent study using FMT in patients with irritable bowel syndrome (IBS) and constipation found transplants persist for up to 2 years, the extent to which the microbiota is alterable in UC is not known. Indeed, there may be particular genetic or immunologic factors in UC leading to selection pressure preventing a change in the microbiota. As an initial step into investigating the potential efficacy of stool transplants for Ulcerative Colitis (UC), the investigators propose to determine the feasibility and stability of transplanted microbiota in a series of 10 patients with mild to moderate UC.

Study Overview

• Status: Terminated
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Other: Fecal Microbiota Transplantation

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98103
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Mild to moderate UC.

Exclusion Criteria:

• Antibiotic exposure in the last 3 months.
• Biologic or immunomodulatory therapy within the last 3 months.
• Corticosteroid therapy or probiotics within the last 2 weeks.
• Severely active disease (defined as Mayo scores of 10 or greater, or patients with endoscopic disease activity scores of 3 or greater).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fecal Microbiota Transplantation; Fecal Microbiota Transplantation by colonoscopic delivery of stool to the right colon.	Other: Fecal Microbiota Transplantation; Fecal microbiota transplantation by colonoscopic administration of 300cc of fecal slurry from healthy donor to the right colon.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful engraftment of donor fecal microbiota at 4 weeks post-transplantation.	Metagenomic shotgun sequencing using Iluminia technology will be used to evaluate for engraftment. Metagenomic data will be analyzed using CompareReads. A % similarity to the recipient > than % similarity to the donor will be defined as engraftment.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Engraftment of fecal microbiota transplantation at 7 days.	As in primary aim but at 7 days.	7 days
Durability of Fecal Microbiota Transplantation at 12 weeks	As in primary aim but at 12 weeks.	12 weeks
Clinical remission at 4 weeks.	Defined as Mayo score <=2 with no subscore >1	4 weeks
Clinical remission at 12 weeks.	Defined as Mayo score <=2 with no subscore >1	12 weeks
Endoscopic remission at 4 weeks.	Mayo endoscopy scope of 0.	4 weeks
Number of patients with worsened disease.	Increase in Mayo score of >2.	4 weeks.
Number of adverse events.		12 weeks.

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: The Broad Foundation
• Investigators: Principal Investigator: Timothy L Zisman, MD, University of Washington

Publications and helpful links

General Publications

• Damman CJ, Miller SI, Surawicz CM, Zisman TL. The microbiome and inflammatory bowel disease: is there a therapeutic role for fecal microbiota transplantation? Am J Gastroenterol. 2012 Oct;107(10):1452-9. doi: 10.1038/ajg.2012.93.
• Damman CJ, Brittnacher MJ, Westerhoff M, Hayden HS, Radey M, Hager KR, Marquis SR, Miller SI, Zisman TL. Low Level Engraftment and Improvement following a Single Colonoscopic Administration of Fecal Microbiota to Patients with Ulcerative Colitis. PLoS One. 2015 Aug 19;10(8):e0133925. doi: 10.1371/journal.pone.0133925. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: November 29, 2012
• First Submitted That Met QC Criteria: December 3, 2012
• First Posted (Estimate): December 5, 2012

Study Record Updates

• Last Update Posted (Estimate): November 13, 2013
• Last Update Submitted That Met QC Criteria: November 11, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: 41454-K