The Optimal Route of Fecal Microbiota Transplantation for Irritable Bowel Syndrome

Study Overview
=================
Brief Summary
-----------------
The object of this study is to find out is there an optimal route for the fecal microbiata transplant (FMT) in patients that suffer from irritable bowel syndrome. The investigators compare outcomes in patients with repeated fecal microbiome samples and make symptomatic questionnaires (i.e. IBS-SSS, GSRS) to find out if there is difference in severity of symptoms compared to FMT given in duodenogastroscopy or in coloscopy.

Detailed Description
-----------------
Irritable bowel syndrome (IBS) is a common functional disorder affecting approximately 10% globally.[1] It is often referred to as benign, although, when severe, may cause significant reduction of quality of life and work absenteeism. The etiology of IBS is unknown although many theories have been proposed. Altered gut motility, epithelial hyperpermeability, low grade inflammation, visceral hypersensitivity, epigenetics and genetics, altered gut-brain interaction and psychological stressors have all been reported in patients with IBS. Several studies have detected alterations in the gut microbiota composition between IBS patients and healthy controls, however a microbiota typical for IBS patients has not been conclusively defined. Fecal microbiota transplantation has over 90% efficace in recurrent Clostridioides difficile infection (rCDI), for which it has been in clinical use for a decade. FMT is currently recommended after the second relapse of rCDI. FMT is recommended to be considered only in clinical trial settings for other indications than rCDI. Randomized controlled studies in FMT for IBS have conflicting results. In studies with a single administration of FMT in colonoscopy a mild transient reduction of IBS symptoms has followed the intervention. In studies with fecal capsules there has not been any benefit observed. FMT via gastroscopy exerted a clear benefit with an up to 89.1% response rate. These surprisingly good results were thought to be contributable to careful donor selection, however the study included only one donor and no specific characteristics of microbiota were indentified of the suspected superdonor. Although all these three administration routes altered the microbiota of IBS patients towards that of the donor, a concurrent decrease in the symptoms was observed only when FMT was administered via colonoscopy or gastroscopy. Manipulation of microbiota through FMT remains to be potential treatment option for IBS, however, several mechanistic questions await answering. Investigators do not yet know what is the component of stool which would carry the healing potential. There needs to be further research to define optimal donors as well as optimal patients who would be prone to benefit of FMT. The amount and number of FMT treatments may be a factor contributing to the outcome. It is also undefined in which extend does the route of administration of FMT contribute to the outcome in IBS patients. Therefore, the investigators present a placebo-controlled trial the optimal route to provide further mechanistic knowledge of the optimal FMT protocol in this patient group.

Official Title
-----------------
The Optimal Route of Fecal Microbiota Transplantation for Irritable Bowel Syndrome

Conditions
-----------------
IBS - Irritable Bowel Syndrome, Microbial Substitution

Intervention / Treatment
-----------------
* Other: Fecal microbiota transplant or plasebo through endoscopy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult 18-70 years known of Finnish language IBS, (new or old diagnosis according to Roma III or IV criteria), all subtypes Informed consent Moderate to severe IBS symptoms, IBS-SSS > 175 Exclusion Criteria: Pregnancy Antibiotic or probiotic treatment, on-going or previous month Abuse of drugs, alcohol or medications Other diagnosis besides IBS causing the GI symptoms, such as IBD, microscopic colitis or bile acid diarrhea

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blinded plasebo controlled study with two treatment cohorts and one plasebo cohort
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FMT through colonoscopy<br>Patient gets FMT in ceacum and plasebo in duodenum. | Other: Fecal microbiota transplant or plasebo through endoscopy<br>* Colonoscopy and gastroscopy<br>|
| Active Comparator: FMT through duodenogastroscopy<br>Patient gets plasebo in ceacum and FMT in duodenum. | Other: Fecal microbiota transplant or plasebo through endoscopy<br>* Colonoscopy and gastroscopy<br>|
| Placebo Comparator: Plasebo<br>Patient gets plasebo in colonoscopy and in gastroscopy. | Other: Fecal microbiota transplant or plasebo through endoscopy<br>* Colonoscopy and gastroscopy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of the different routes of FMT, for alteration of gut microbiota towards that of the donor. | The changes in the engraftment of specific bacteria between the active groups is of special interest, and the changes in the microbiota during the whole of study in the intervention group and in the plasebo group. | Microbiota is tested at prescreening visit, at the baseline and in 4, 12 and 52 weeks after FMT-procedure. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The main clinical outcome is reduction of abdominal pain three months after FMT. | Gut pain: Has your abdominal pain reduced after the intervention? Broadening of diet: Have you been able expand your diet after the intervention? Global IBS symptoms: reduction of IBS-SSS total score 50 points or more from the baseline value | 3 months | 
| GI Symptoms: THE GASTROINTESTINAL SYMPTOM RATING SCALE (GSRS) | Change in symptoms in GSRS questionnaire. Scale from 0 to 90, lower the score better the outcome. | in 3 months and in 1 year points compared to baseline. | 
| Mood, General Anxiety-Disorder 7 - questionnaire | Mood changes in GAD -questionnaire. Aim is to lower the score in GAD-7 questionnaire. | The change in the score of questionnaires between the baseline at 3 months and 12 months | 
| Mood, Beck's Depression Inventory. | Mood changes in BDI -questionnaire. Score from 0-60. Aiming to lower the score in BDI-questionnaire. | The change in the score of questionnaires between the baseline at 3 months and 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IBS, FMT, Fecal microbiota transplant, microbiome