Refined Fecal Microbiota Transplantation (FMT) for Ulcerative Colitis (UC) (REFOCUS)

REFOCUS: Refined Fecal Microbiota Transplantation (FMT) Delivered by Oral Capsules for Induction of Remission in Mild to Moderate Ulcerative Colitis - a Phase I Study

The researchers intend to prospectively study the safety, clinical efficacy and microbial outcomes in patients with recently diagnosed UC with FMT capsule therapy derived from pre-defined donors. Donors will be specifically screened for Fusobacterium and Sutterella species as well as for global diversity. It is unknown if treatment with antibiotics before FMT improves the engraftment and/or efficacy of FMT in UC, therefore the researchers plan to randomize subjects to receive pre-treatment with antibiotics or not before FMT therapy. The research team enroll patients from The Susan and Leonard Feinstein IBD Center and our established early diagnosis clinic at Mount Sinai Hospital (MSH).

Study Overview

• Status: Terminated
• Conditions: Ulcerative Colitis; FMT; Fecal Microbiota Transplant
• Intervention / Treatment: Drug: Placebo; Drug: Metronidazole; Drug: Vancomycin; Biological: Fecal Microbiota Transplantation

Detailed Description

This is an open-label two arm pilot study to measure the safety, microbiological and clinical impacts of FMT in patients with ulcerative colitis. The researchers will prospectively enroll 16 UC patients (up to 20 subjects accounting for subjects dropping out) with moderate-severe disease from one tertiary care referral center. The overall objective of the study is to collect robust clinical data and create a tissue repository including blood, stool and biopsies to understand the safety, efficacy and microbial changes FMT has on UC patients. The central hypothesis is that pre-defined oral capsule administered FMT is safe and effective for the treatment of UC.

Objectives: To determine the tolerability, feasibility, and safety of using fecal microbiota transplantation orally as an induction agent for patients with ulcerative colitis. To determine whether fecal microbiota transplantation (FMT) delivered via oral capsules can induce clinical remission in patients with mild to moderate ulcerative colitis. Assess whether pretreatment with antibiotics improves engraftment and efficacy of FMT in UC. To characterize the impact of orally administered FMT on the microbiota of patients with ulcerative colitis, particularly those changes associated with response or lack of response.

Study Outcomes: Clinical remission at Week 8, defined as: Steroid-free clinical remission (Total Mayo less 2) and Endoscopic remission (Mayo endoscopic subscore 0 or 1)

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

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

Description

• Adults aged 18 to 75 with UC, with initial diagnosis of UC >3 months prior to time of study enrollment visit
• Partial Mayo score of 4-10 with endoscopic subscore ≥2 on flexible sigmoidoscopy
• Permissible UC medications include oral or rectal administered mesalamines
• Corticosteroids must be discontinued at least 4 weeks before enrollment
• Documented negative C. difficile and GI PCR for enteric pathogens (BioFire) testing before commencement of fecal microbiota transplantation
• Previous documentation of ulcerative colitis based on colonoscopy/flexible sigmoidoscopy with compatible histology

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: FMT with Antibiotics; Participants will receive antibiotics before receiving Fecal Microbiota Transplantation	Drug: Metronidazole; Antibiotic treatment - 250 mg every 6 hrs for 5 days; Other Names: Flagyl; Drug: Vancomycin; Antibiotic treatment - 125 mg every 6 hrs for 5 days; Biological: Fecal Microbiota Transplantation; Encapsulated biologically active human fecal material (donor stool) is provided in capsule form. The fecal material is homogenized with sterile saline, then pelleted and re-suspended in sterile saline/40% glycerol. Participants will receive 15 FMT capsules per day for 3 consecutive days. Capsule are to be swallowed under direct supervision.; Other Names: FMT
Placebo Comparator: FMT with placebo; Participants will receive placebo before receiving Fecal Microbiota Transplantation	Drug: Placebo; Placebo treatment; Biological: Fecal Microbiota Transplantation; Encapsulated biologically active human fecal material (donor stool) is provided in capsule form. The fecal material is homogenized with sterile saline, then pelleted and re-suspended in sterile saline/40% glycerol. Participants will receive 15 FMT capsules per day for 3 consecutive days. Capsule are to be swallowed under direct supervision.; Other Names: FMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with an adverse	Safety as measured by proportion of participants with an adverse event through week 8	8 Weeks
Proportion of participants with a severe adverse	Safety as measured by proportion of participants with a severe adverse event through week 8	8 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients requiring escalation of medical therapies	Number of patients requiring escalation of medical therapies based on clinical relapse. Clinical relapse is defined by requiring additional medical therapy.	8 weeks
Proportion of patients that achieve Mayo score 0 or 1	Proportion of patients with initial Mayo 2/3 disease at flexible sigmoidoscopy that achieve endoscopic improvement (Mayo score 0 or 1). The Mayo Score is a composite of subscores (each rated 0-3) from four categories, including stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy or colonoscopy, and physician's global assessment, with a total score ranging from 0-12, with higher score indicating worse health outcomes.	8 weeks
Number of patients with endoscopic remission	Number of patients with endoscopic remission as defined by a Mayo score of 0	8 weeks
Change in Nancy score	Change in histological score assessed by the Nancy score. The Nancy score includes 3 histologic items that define 5 grades of activity: absence of significant histologic disease, chronic inflammatory infiltrate with no acute inflammatory infiltrate, mildly active disease, moderately active disease, and severely active disease. The Nancy index is defined by a 5-level classification ranging from grade 0 (absence of significant histological disease activity) to grade 4 (severely active disease). higher score indicating worse health outcomes.	8 weeks
Fecal calprotectin level	Mean change fecal calprotectin levels	baseline and 8 weeks
C-reactive protein levels	Mean change C-reactive protein levels	baseline and 8 weeks
Hemoglobin levels	Mean change hemoglobin levels	baseline and 8 weeks
Albumin levels	Mean change albumin levels	baseline and 8 weeks
ESR level	Mean change erythrocyte sedimentation rate (ESR)	baseline and 8 weeks

Collaborators and Investigators

• Sponsor: Ari M Grinspan
• Investigators: Principal Investigator: Ari Grinspan, MD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2021
• Primary Completion (Actual): August 22, 2022
• Study Completion (Actual): August 22, 2022

Study Registration Dates

• First Submitted: July 9, 2021
• First Submitted That Met QC Criteria: July 9, 2021
• First Posted (Actual): July 20, 2021

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Fecal Microbiota Transplantation; FMT; Ulcerative colitis; UC; Fecal Microbiota Transplant; Fecal Matter Transplant
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Vancomycin; Metronidazole
• Other Study ID Numbers: GCO 18-1464

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is not a plan to make IPD available

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No