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

Ulcerative Colitis Clinical Trial

— REFOCUS  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04968951
• Other study ID #: GCO 18-1464
• Status: Terminated
• Phase: Early Phase 1
• Start date: November 10, 2021
• Est. completion date: August 22, 2022

Study information

• Verified date: February 2024
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: August 22, 2022
• Est. primary completion date: August 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

• 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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Fecal Microbiota Transplant
• FMT
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Metronidazole
Antibiotic treatment - 250 mg every 6 hrs for 5 days
• Placebo
Placebo treatment
• 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.

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Ari M Grinspan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants with an adverse	Safety as measured by proportion of participants with an adverse event through week 8	8 Weeks
Primary	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	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
Secondary	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
Secondary	Number of patients with endoscopic remission	Number of patients with endoscopic remission as defined by a Mayo score of 0	8 weeks
Secondary	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
Secondary	Fecal calprotectin level	Mean change fecal calprotectin levels	baseline and 8 weeks
Secondary	C-reactive protein levels	Mean change C-reactive protein levels	baseline and 8 weeks
Secondary	Hemoglobin levels	Mean change hemoglobin levels	baseline and 8 weeks
Secondary	Albumin levels	Mean change albumin levels	baseline and 8 weeks
Secondary	ESR level	Mean change erythrocyte sedimentation rate (ESR)	baseline and 8 weeks