Fecal Microbiota Transplantation for IBS

Efficacy and Safety of Proteolytic Activity-Guided Fecal Microbiota Transplantation for Irritable Bowel Syndrome (PRAGMAT Trial)

The purpose of this study is to learn the efficacy and safety of fecal microbiota transplantation (FMT) using stool from a donor with low proteolytic activity and containing the bacteria Alistipes putredinis in patients with post-infection irritable bowel syndrome (PI-IBS) and high proteolytic activity. Proteolytic activity is the breakdown of proteins into smaller polypeptides or amino acids.

Study Overview

• Status: Recruiting
• Conditions: Irritable Bowel Syndrome; Diarrhea
• Intervention / Treatment: Biological: Donor Fecal Microbiota Transplantation; Biological: Autologous Fecal Microbiota Transplantation

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Margaret Breen-Lyles; Phone Number: 507-293-0237; Email: Breen-Lyles.Margaret@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Campylobacter PI-IBS defined by Rome III or Rome IV criteria
• Non IBS-C
• Moderate to severe symptoms defined by IBS-SSS≥175
• Able to safely undergo and consent to colonoscopy

Exclusion Criteria

• Immune deficiency or treatment with immunosuppressive medications
• Severe bowel or medical disease precluding administration of bowel prep
• Severe bowel or medical disease precluding colonoscopy with conscious sedation
• Active cancer
• Pregnant or lactating
• Abdominal surgery (exception of fundoplication, hernia, appendectomy, cholecystectomy, caesarean section and hysterectomy)
• Severe psychiatric disorder (HADS-A or D>16), or diagnosed alcohol or drug abuse disorder
• New probiotics or treatment with antibiotics, NSAIDs (within 4 wks prior to study entry)
• Use of treatments known to affect colonic motility (with exception of loperamide)
• Diagnosed h/o bleeding disorder
• Organic GI diseases (IBD, celiac disease, microscopic colitis)
• Chronic kidney or liver disease
• Absolute neutrophil count (ANC) <500 IU/ml

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
Experimental: Donor Fecal Microbiota Transplantation Group; Subjects will receive a fecal microbiota transplantation (FMT) using stool from a donor	Biological: Donor Fecal Microbiota Transplantation; Single fecal microbiota transplantation using 50 gm of freeze-thawed donor stool
Placebo Comparator: Autologous Fecal Microbiota Transplantation Group; Subjects will receive a fecal microbiota transplantation (FMT) using their own stool	Biological: Autologous Fecal Microbiota Transplantation; Single fecal microbiota transplantation using 50 gm of stool collected from the same individual

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of responders	Number of subjects receiving the donor fecal microbiota transplantation identified as a responder defined as a decrease of ≥50 points in Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) from baseline. The Irritable Bowel Syndrome Symptom Severity Score scale has a possible range of scores from 0-500. Mild cases are classified as a score of 75-175, moderate cases are classified as a score of 175-300, and severe cases are classified as a score of >300.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in level of fecal proteolytic activity	The level of fecal proteolytic activity will be measured at baseline and again at 12 weeks. The proteolytic activity is measured using a standardized FITC Casein assay that relies on the activity of proteases in the sample to digest casein protein.	Baseline, 12 weeks
Changes in in vivo excretion of 2-24 hr lactulose excretion	Measured by permeability testing	Baseline, 12 weeks
Number of weekly responders	Number of subjects to meet responder criteria of ≥30% decrease in average of worst abdominal pain in past 24 hours plus ≥50% decrease in the number of days per week with at least one stool that has a consistency of Type 6 or 7 (compared with baseline)	12 weeks
Global Adequate Relief Questionnaire	Number of subjects to report adequate relief of IBS symptoms, measured by answering yes to question "In the past 7 days have you had adequate relief of your IBS symptoms?"	12 weeks
Alistipes putredinis proportion post-FMT	Number of subject to have the bacteria Alistipes putredinis in stool sample after fecal microbiota transplantation (FMT)	12 weeks

Collaborators and Investigators

• Sponsor: Madhusudan (Madhu) Grover, MBBS
• Investigators: Principal Investigator: Madhusudan Grover, MBBS, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: March 1, 2023
• First Submitted That Met QC Criteria: March 17, 2023
• First Posted (Actual): March 20, 2023

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Post-infection irritable bowel syndrome with diarrheal; Post-infection irritable bowel syndrome with mixed symptoms
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Diarrhea
• Other Study ID Numbers: 22-005385

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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