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

Early Phase 1
Terminated
Conditions
Ulcerative Colitis
FMT
Fecal Microbiota Transplant
Interventions
Drug: Placebo
Drug: Metronidazole
Drug: Vancomycin
Biological: Fecal Microbiota Transplantation
Registration Number
NCT04968951
Lead Sponsor
Ari M Grinspan
Brief 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).

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)

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
4
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
FMT with AntibioticsVancomycinParticipants will receive antibiotics before receiving Fecal Microbiota Transplantation
FMT with AntibioticsFecal Microbiota TransplantationParticipants will receive antibiotics before receiving Fecal Microbiota Transplantation
FMT with placeboPlaceboParticipants will receive placebo before receiving Fecal Microbiota Transplantation
FMT with placeboFecal Microbiota TransplantationParticipants will receive placebo before receiving Fecal Microbiota Transplantation
FMT with AntibioticsMetronidazoleParticipants will receive antibiotics before receiving Fecal Microbiota Transplantation
Primary Outcome Measures
NameTimeMethod
Proportion of participants with an adverse8 Weeks

Safety as measured by proportion of participants with an adverse event through week 8

Proportion of participants with a severe adverse8 Weeks

Safety as measured by proportion of participants with a severe adverse event through week 8

Secondary Outcome Measures
NameTimeMethod
Number of patients requiring escalation of medical therapies8 weeks

Number of patients requiring escalation of medical therapies based on clinical relapse. Clinical relapse is defined by requiring additional medical therapy.

Proportion of patients that achieve Mayo score 0 or 18 weeks

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.

Number of patients with endoscopic remission8 weeks

Number of patients with endoscopic remission as defined by a Mayo score of 0

Change in Nancy score8 weeks

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.

Fecal calprotectin levelbaseline and 8 weeks

Mean change fecal calprotectin levels

C-reactive protein levelsbaseline and 8 weeks

Mean change C-reactive protein levels

Hemoglobin levelsbaseline and 8 weeks

Mean change hemoglobin levels

Albumin levelsbaseline and 8 weeks

Mean change albumin levels

ESR levelbaseline and 8 weeks

Mean change erythrocyte sedimentation rate (ESR)

Trial Locations

Locations (1)

Icahn School of Medicine at Mount Sinai

🇺🇸

New York, New York, United States

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