Fecal Microbiota Transplantation for IBS

Study Overview
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Brief Summary
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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.

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

Conditions
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Irritable Bowel Syndrome, Diarrhea

Intervention / Treatment
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* Biological: Donor Fecal Microbiota Transplantation
* Biological: Autologous Fecal Microbiota Transplantation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donor Fecal Microbiota Transplantation Group<br>Subjects will receive a fecal microbiota transplantation (FMT) using stool from a donor | Biological: Donor Fecal Microbiota Transplantation<br>* Single fecal microbiota transplantation using 50 gm of freeze-thawed donor stool<br>|
| Placebo Comparator: Autologous Fecal Microbiota Transplantation Group<br>Subjects will receive a fecal microbiota transplantation (FMT) using their own stool | Biological: Autologous Fecal Microbiota Transplantation<br>* Single fecal microbiota transplantation using 50 gm of stool collected from the same individual<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-infection irritable bowel syndrome with diarrheal, Post-infection irritable bowel syndrome with mixed symptoms