Fecal Microbiota Transplant in the Treatment of Ulcerative Colitis (FMTUC)

The purpose of this study is to evaluate the effectiveness of Fecal Microbiota Transplant (FMT) for treating patients with mild to moderate Ulcerative Colitis (UC). Even with the expanding choices of medication for UC, physicians and patients are still in search of highly effective and safe medications with minimal side effects. FMT has been approved for the treatment of a bacterial infection called Clostridium difficile. In this setting, FMT has been proven to be an effective and safe alternative therapy with zero reported serious adverse events from patients that have had this treatment.

The providers that are conducting this study hypothesize that delivering microbes from a healthy human gut can help treat the damages caused by UC. This is done by "transplanting" fecal material, which contains a highly complex and dense community of healthy microbes, including bacteria, fungi and viruses. This collection of microbes is referred to as a microbiome. Preliminary studies suggest that alteration of the microbiome can help treat UC.

Study Overview

• Status: Unknown
• Conditions: Ulcerative Colitis, Active Moderate
• Intervention / Treatment: Biological: Placebo; Biological: Fecal Microbiota Transplant

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Vermont
    • Burlington, Vermont, United States, 05401
      • The University of Vermont Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men or women 18-75 years of age.
• Established diagnosis of ulcerative colitis (UC) with known involvement of the left colon
• Mild to moderate disease defined as endoscopic evidence of disease with Mayo endoscopic sub-score 1 or 2 and total MAYO score ranging from 4-10. (The Mayo score ranges from 0 to 12, with higher scores indicating more severe disease. This score can be used for both initial evaluation and monitoring treatment response).
• Patients may be on any class of IBD-related medication (excluding steroids)
• Patients must be on stable medication regimen for at least 6 weeks prior to enrollment.
• Ability to understand and willingness to sign informed consent document

Exclusion Criteria:

• Patient who are asymptomatic
• Patients with severe, refractory disease (defined as Mayo scores of > 10, or endoscopic disease activity score of > 3) or patients with any other significant condition which, in the opinion of the investigator, could confound or interfere with evaluation of safety, tolerability of the investigational treatment or prevent compliance with the study protocol
• Prior colectomy
• Positive stool test for any of the following: Clostridium difficile by PCR, Salmonella, Shigella, Yersinia, Campylobacter, enteropathogenic E. coli by standard stool culture.
• Use of the steroid medications (any formulation) in the prior 6 weeks to enrollment
• Systemic antibiotic use within prior 6 weeks to enrollment
• Regular probiotic supplement use within prior 48 hours to enrollment
• Pregnancy or breastfeeding
• Severe immunodeficiency, inherited or acquired (e.g. HIV, chemotherapy, or radiation therapy)
• History of anaphylaxis (severe allergic reaction)
• Documented allergy to fluoroquinolones, metronidazole
• Life expectancy less than 12 months
• Age less than 18 or greater than 75 years of age
• History of esophageal or gastric motility disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Control; Sham FMT and Sham Microbial Maintenance plus standard therapy	Biological: Placebo
Experimental: Treatment; FMT and microbial maintenance plus standard therapy	Biological: Fecal Microbiota Transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Asses Endoscopic Stages of the Colon Pre/Post FMT	Assess endoscopic stage of the inflamed colon (endoscopic Mayo score) and assess the histologic stage of the biopsied colon (quiescent/mild/moderate/severe) pre and post FMT.	2 years
Asses Biologic Inflammatory Markers	Assess biologic inflammatory markers (ESR, CRP, fecal calprotectin, and fecal lactoferrin) pre and post FMT.	2 years
Review and Track Patient reported Outcomes via Validated Questionnaires	Assess patient-report outcomes (symptomatology and quality of life) calculated via validated questionnaires (symptomatic Mayo Score and SF36)	2 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in metagenomic sequencing in Stool samples after FMT treatment	Trace the effect FMT therapy has on microbiome diversity and to track whether this effect is sustained during and after therapy via metagenomic sequencing of stool samples at time 0, and weeks 6, 12, and 18.	After 6, 12, and 18 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Asses changes in T-cell measures and serotonin signaling in mucosal biopsy samples and peripheral blood samples	Explore potential therapeutic mechanisms of FMT therapy. Changes in the host immune response before and after treatment will be assessed via measurement of both mucosal and peripheral T-cells populations (Th1, Th2, Th17) using mucosal biopsies and blood samples respectively.Changes in mucosal serotonin signaling will be measured using mucosal biopsies.	2 years

Collaborators and Investigators

• Sponsor: University of Vermont
• Investigators: Principal Investigator: Peter L Moses, MD, The University of Vermont Medical Center

Publications and helpful links

General Publications

• Crothers JW, Chu ND, Nguyen LTT, Phillips M, Collins C, Fortner K, Del Rio-Guerra R, Lavoie B, Callas P, Velez M, Cohn A, Elliott RJ, Wong WF, Vo E, Wilcox R, Smith M, Kassam Z, Budd R, Alm EJ, Mawe GM, Moses PL. Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study. BMC Gastroenterol. 2021 Jul 8;21(1):281. doi: 10.1186/s12876-021-01856-9.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): December 1, 2017
• Study Completion (Anticipated): September 1, 2018

Study Registration Dates

• First Submitted: February 19, 2015
• First Submitted That Met QC Criteria: March 16, 2015
• First Posted (Estimate): March 17, 2015

Study Record Updates

• Last Update Posted (Actual): July 9, 2018
• Last Update Submitted That Met QC Criteria: July 6, 2018
• Last Verified: July 1, 2018

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: 15373