Clinical trial NCT02154867: Fecal Microbial Transplantation in Treatment of Irritable Bowel Syndrome; a Double Blinded Placebo Controlled Trial.
Official title: Recalibrating Intestinal Microflora in IBS by Fecal Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Irritable Bowel Syndrome
Keywords: IBS-D
FMT
metagenomics
gut microbiome
Lead sponsor: University Hospital of North Norway
Sponsor class: OTHER
First posted: 2014-06-03
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in subjective symptom score
timeFrame: at 0 and 3 months
Secondary outcomes:
measure: Microbiome profile change
timeFrame: at 0, 3 and 12 months
measure: Long term effects of fecal transplantation
timeFrame: at 12 months
measure: Safety of fecal transplantation in IBS
timeFrame: during study period (0-12 months)
Other outcomes:
Locations:
city: Harstad
country: Norway
facility: University Hospital of North Norway
Study officials:
affiliation: University Hospital of North Norway
name: Rasmus Goll, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of North Norway
name: Per C Valle, PhD
role: STUDY_DIRECTOR
References:
citation: Goll R, Johnsen PH, Hjerde E, Diab J, Valle PC, Hilpusch F, Cavanagh JP. Effects of fecal microbiota transplantation in subjects with irritable bowel syndrome are mirrored by changes in gut microbiome. Gut Microbes. 2020 Nov 9;12(1):1794263. doi: 10.1080/19490976.2020.1794263.
citation: Johnsen PH, Hilpusch F, Cavanagh JP, Leikanger IS, Kolstad C, Valle PC, Goll R. Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial. Lancet Gastroenterol Hepatol. 2018 Jan;3(1):17-24. doi: 10.1016/S2468-1253(17)30338-2. Epub 2017 Nov 1.