Fecal Microbial Transplantation in Treatment of Irritable Bowel Syndrome; a Double Blinded Placebo Controlled Trial.

Study Overview
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Brief Summary
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Fecal Microbial Transplantation in Treatment of Irritable Bowel Syndrome; a Double Blinded Placebo Controlled Trial - the REFIT project Irritable bowel syndrome (IBS) is a condition characterized by variable complaints like diarrhoea, bloating and abdominal pain, and may result in considerably reduced quality of life and increased sickness absence. The prevalence of IBS in the general population may be as high as 15 per cent depending on the diagnostic criteria used. The pathophysiology of IBS is poorly understood and theories of visceral hypersensitivity, micro-inflammation and other less well founded theories have been stated. So far, no measurement or test can affirm diagnosis, but exclusion of organic diseases in combination with a typical symptom pattern according to the Rome classification can set the diagnosis. Earlier non-controlled case reports have shown a convincing effect of fecal microbial transplantation (FMT) in IBS patients. However, no placebo controlled trial has been performed in this condition. Changes in the gut microbiome may be an important factor in IBS pathogenesis. Microbiome analysis has revealed changes in microbiome composition that may trigger changes in visceral sensibility and pain perception. The fecal microbial transplantation (FMT) procedure has been used primarily to treat clostridium difficile infections. Few minor side effects have been reported. Hypothesis: IBS is caused by an imbalance of the gut microbiome that may be reset by transplanting a microbiome sample from a healthy donor. Aim of study: To test the clinical effect of FMT in patients with IBS To describe the fecal microbiome in IBS patients To describe changes in the fecal microbiome of IBS patients following FMT The REFIT study will perform a randomized placebo-controlled double blinded trial of FMT on IBS according to the Rome 3 criteria. A study group of 60 IBS (diarrhoea variant) patients will recruited from general practice and allocated to active (30) or placebo (30) by block randomization. Donors will be 15 healthy volunteers with no risk behaviour and a pre-screening for communicable diseases will be performed. Outcome measures will be clinical assessment by IBS-severity scoring system (IBS-SSS) at 0, 1, 3, 6, and 12 months. Microbiome analysis will be performed by metagenomic sequencing (University of Tromsø) at 0, 3, and 12 months for patients, and at inclusion for donors.

Official Title
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Recalibrating Intestinal Microflora in IBS by Fecal Transplantation

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Biological: Fecal transplantation
* Other: Placebo fecal transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for patients: Patients with IBS-D according to Roma 3 criteria Exclusion Criteria for patients: Immunomodulating medication Nocturnal abdominal pain Constant abdominal pain Alarm symptoms like rectal bleeding, weight loss, nightsweats Symptomatic heart/vascular/lung disease Renal failure Known food allergy Microscopic/collagenous colitis non-compliant BMI <18 Inclusion criteria for donors: healthy volunteers Exclusion criteria for donors Tattoos, imprisoning or piercing last 3 months Any history of chronic diarrhoea, constipation, inflammatory bowel disease, irritable bowel disease, colorectal polyps or cancer, immunosuppression, morbid obesity, metabolic syndrome, atopica, or fatigue positive test for hepatitis B, C, HIV, treponema pallidum sexual high risk habits antibiotic treatment in the past 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fecal transplantation<br>Fecal transplantation of freshly prepared feces from healthy donor. Application by colonoscope in proximal half of colon. | Biological: Fecal transplantation<br>* Preparation of flesh feces by blending in 0.9 % saline and crude filtering. The solution is applied in proximal colon of IBS patient by colonoscopy after standard bowel preparation.<br>* Other names: Fecal microbial transplantation;|
| Placebo Comparator: Placebo fecal transplantation<br>Sham transplant subject's own feces. Application by colonoscope in proximal part of colon. | Other: Placebo fecal transplant<br>* Fecal transplantation with own feces<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in subjective symptom score | Comparison of Irritable bowel syndrome severity scoring system (IBS-SSS) grade assessment before and after fecal transplantation | at 0 and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiome profile change | Characterization of fecal microbiome by metagenomic analysis before and after intervention | at 0, 3 and 12 months | 
| Long term effects of fecal transplantation | Assessment of symptom burden by IBS-SSS | at 12 months | 
| Safety of fecal transplantation in IBS | Registration of any adverse events. If any serious adverse events are encountered, the study group and local ethics committee will evaluate if study should be terminated. | during study period (0-12 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FMT, IBS-D, metagenomics, gut microbiome