The objective of this protocol is to evaluate the efficacy of fecal microbiota transplantation (FMT) using oral capsules containing frozen stools vs sham FMT on IBS severity score at 12 weeks in patients with severe irritable bowel syndrome refractory to conventional treatments.
Irritable bowel syndrome (IBS) is a chronic disease. It affects about 4.4 to 10 % of the French general population (according to Rome III or Rome IV definition) and is the most frequent functional bowel disorder in patients visiting general practitioners or gastroenterologists. The efficacy of treatments is often limited, in particular form the case severe of IBS (IBS-SSS\>300) which concerns at least 20 to 25% of patients and IBS can cause significant deterioration in quality of life. In this context, microbiota could become a potential therapeutic target, and replacement of the abnormal fecal microbiota by an "healthy" one, especially in patients refractory to previous treatment and with severe symptoms, is a seducing new therapeutic strategy. The primary outcome is an improvement in the IBS-SSS score level at 12 weeks after taking a oral capsules of FMT in patients with severe IBS.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
150
Oral, capsulized, frozen fecal microbiota transplantation FMT delivering approximatively 24 g of stools taken in one day in two separate meals. Administration of the FMT after colon cleaning.
Oral, capsulized, frozen capsules without fecal matter but containing cryopreservation solution will be administered at the same volume and same time point as in the experimental group. Taken in one day in two separate meals. Administration of the sham after colon cleaning.
Gastro-enterology department, Avicenne Hospital
Bobigny, France
Decrease in IBS severity at 12 weeks defined by the percentage of patients having at least a 75 points decrease in IBS-SSS.
To evaluate the efficacy of oral capsules containing frozen fecal microbiota (FMT) vs sham FMT on IBS severity score at 12 weeks in patients with irritable bowel syndrome with severe disease refractory to conventional treatments. Decrease in IBS severity at 12 weeks is defined by the percentage of patients having at least a 75 points decrease in IBS-SSS.
Time frame: At 12 weeks
Decrease in IBS severity at 12 weeks defined by the percentage of patients having at least a 50 points decrease in IBS-SSS.
To evaluate the efficacy of oral capsules containing frozen fecal microbiota (FMT) vs sham FMT on IBS severity score at 12 weeks in patients with irritable bowel syndrome with severe disease refractory to conventional treatments (at least a 50 points decrease in IBS-SSS)
Time frame: At 12 weeks
FMT success
patient's microbiota 12 weeks after FMT closer to that of the donor than the patient's microbiota before FMT. The composition of the patient's fecal microbiota 12 weeks after FMT will be compared to the patient's microbiota before transplantation and to the donor using the Sorensen similarity index. The FMT will be considered as a success if the Sorensen index \[patient after FMT vs donor\] \> Sorensen index \[patient after FMT vs patient before FMT\] and if the Sorensen index \[patient after FMT vs donor\] ≥ 0,6. The composition of fecal microbiota will be measured by pyrosequencing (16S RNA).
Time frame: At 12 weeks
Intestinal microbiota composition at week 12 and 24 by 16s sequencing.
Intestinal microbiota composition and diversity at week 12 and 24 assessed by 16s sequencing. Microbiota composition and diversity assessed by 16s sequencing at week 12 and 24, compared to baseline and to healthy volunteers donor's microbiota. Microbiota composition will be assessed using Qiime pipeline and analyzed at all phylogenetic levels. Diversity will be evaluated using Shannon index, Simpson index, Chao1 index and number of observed species.
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Time frame: at week 12 and 24
Efficacy (decrease in IBS severity >75 points) at week 24 according to FMT success.
Efficacy (decrease in IBS severity \>75 points) according to FMT success.
Time frame: At 24 weeks
EMA Endpoint at week 12 and 24 defined as a patient who fulfils the response criteria (simultaneous improvement of transit and abdominal pain) displayed in the following for at least 50% of the observation time.
Efficacy according to EMA (European Medical Agency) endpoint in IBS on composite criteria at 12 or 24 weeks
Time frame: at week 12 and 24
Percentage of responders in the different subgroups IBS-D, IBS-C and IBS-M using the primary endpoint at week 12 and 24.
IBS severity at 12 weeks by donors (one donor giving FMT to several patients)
Time frame: at week 12 and 24
Mean IBS-SSS (IBS severity), comparison between FMT and placebo at 12 and 24 weeks)
IBS severity at 12 weeks and at 24 weeks by IBS subtypes according to transit pattern. The score ranges from 0 to 500 ( Remission : 0 to 74, Mild : 75 to 175, Moderate : 175 to 300 and Severe : \>300).
Time frame: at week 12 and 24
Mean IBS-QoL score (IBS Quality of life) comparison between FMT and placebo at 12 and 24 weeks (Drossman et al. 2000)
IBS Quality of life at 12 weeks and 24 weeks. Irritable Bowel Syndrom- Quality of Life (IBS-QoL) at 12 weeks and 24 weeks, IBS-QoL ranges from 0 ( worse) to 100 (better).
Time frame: at week 12 and 24
Patient's perception of FMT : - Questionnaire for correct assessment of FMT or placebo and FMT acceptability) at V2 (FMT administration). - Questionnaire for assessment of FMT secondary effects at V3.
Patient's perception of FMT (questionnaire for correct assessment of FMT or placebo and FMT acceptability) (Annex D), secondary effects of FMT
Time frame: V2: five weeks after inclusion. V3:Four weeks after V2
Safety (Serious Adverse Events, Adverse Events) compared between groups.
Safety (Serious Adverse Events, Adverse Events) compared between groups.
Time frame: through study completion, at 24 months