Allogeneic Microbiota-reconstitution (AMR) in Diarrhea-predominant Irritable Bowel Syndrome (IBS-D)

Study Overview
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Brief Summary
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The investigators will perform a multicenter, 2:1 randomized, double-blinded, placebo-controlled trial of AMR in patients with diarrhea predominant-IBS (IBS-D) diagnosed according to Rome III criteria and the IBS-QOL questionnaire. Central supply and quality control of donor material will be used to control bias. Primary endpoint is improvement of IBS-SSS (Severity Score System) compared to baseline. Secondary endpoints include changes in IBS-QOL, short term safety and one year follow up to control long term effects, safety and changes in and acceptance of donor microbiome after AMR using16S rDNA sequencing and quantitative diversity analysis.

Detailed Description
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This study assesses allogeneic microbiota reconstitution (AMR) as novel treatment to improve symptoms and quality of life of patients with diarrhea-predominant irritable bowel syndrome (IBS-D). The investigators will perform a prospective multicenter, 2:1 randomized, double-blinded, placebo-controlled trial of AMR in patients with IBS-D diagnosed according to Rome III criteria and the IBS-QOL questionnaire. The experimental intervention is an infusion of donor feces via gastroscopy. The placebo intervention is an infusion of sterile saline via gastroscopy. Planned number of patients included in the study: 42 patients Planned per-protocol group: 33 patients

Official Title
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Allogeneic Microbiota-reconstitution (AMR) for the Treatment of Patients With Diarrhea-predominant Irritable Bowel Syndrome - the AMIRA Trial

Conditions
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Diarrhea-predominant Irritable Bowel Syndrome

Intervention / Treatment
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* Procedure: Allogeneic microbiota reconstitution
* Procedure: Placebo-Allogeneic microbiota reconstitution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written informed consent irritable bowel syndrome of diarrhea-predominant type according to ROME III criteria Symptoms for > 1 year before study inclusion persisting symptoms > 1 year before study inclusion relevant symptoms with reduced Quality of Life (IBS-QOL < 60 Points) no specific findings in gastroscopy and colonoscopy with biopsies in the last 2 years Exclusion Criteria: chronic inflammatory diseases gastrointestinal infectious diseases microscopic colitis celiac disease diarrhea caused by fructose- or lactose intolerance gastrointestinal malignancies or intestinal polyps irritable bowel syndrome of other type than IBS-D bile acid diarrhea constipation symptoms caused by other diseases than IBS-D dementia abdominal surgery in the last months antibiotic therapy in the last 3 months pregnancy linguistic barrier for informed consent

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

Sexes Eligible for Study
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All

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verum-AMR<br>Patients receiving Verum-Allogeneic Microbiota Reconstitution via gastroscopy | Procedure: Allogeneic microbiota reconstitution<br>* gastroscopic microbiota Infusion (Verum)<br>|
| Placebo Comparator: Placebo-AMR<br>Patients receiving Placebo(Saline)-Infusion via gastroscopy | Procedure: Placebo-Allogeneic microbiota reconstitution<br>* gastroscopic saline Infusion (placebo)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease of the IBS-SSS questionnaire > 105 Points compared to baseline |  | 90 days after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of IBS-QOL using IBS-QOL-questionnaire compared to baseline |  | 90 days and 1 year after intervention | 
| Changes and acceptance of donor microbiome (16S rDNA-analysis) | 16S rDNA-analysis for microbiome biodiversity, correlation to IBS-Symptom Severity Score (IBS-SSS) | 90 days after intervention | 
| Number of participants with treatment related adverse events |  | follow-up 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allogeneic microbiota reconstitution, diarrhea-predominant irritable bowel syndrome, microbiome