Study of Fecal Microbiota Transplantation (FMT) in Severe IBS Patients

Phase 3

Not yet recruiting

• Conditions: Irritable Bowel Syndrome
• Interventions: Drug: Administration of the sham (PLACEBO); Drug: Administration of fecal microbiota transplantation ( FMT capsules)

• Registration Number: NCT06433180
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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.

Detailed Description

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 Timeline

• Status Verified: 2024-04
• Study First Submitted: 2024-05-13
• Study First Submitted QC: 2024-05-26
• Last Update Submitted: 2024-05-26
• Study First Posted: 2024-05-29
• Last Update Posted: 2024-05-29
• Study Start: 2024-06-01
• Primary Completion: 2028-07-15
• Study Completion: 2029-07-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• Age ≥ 18 years and < 75 years
• IBS defined according to Rome IV definition (IBS-C, IBS-D or IBS-M)
• Severe disease (IBS-SSS >300) and refractory to at least two previous treatment strategies:among the following : anti-spasmodic and/or laxatives (polyethylene glycol) or anti-diarrheal drug (loperamide) according to transit subtype for one month, antidepressants for 2 months, probiotics (ALFLOREX, SMEBIOCTA, PROBIOLOG FLORVIS) for 1 month, hypnosis for 5 hypnosis sessions in two months, Cognitive Behavioral Therapies for 2 months, colestyramine for IBS-D patients for 1 month, ondansetron for IBS-D patients and for 1 month, ebastine for 2 months, L-glutamine (5g x3/day, for 2 months, Gelsectan for one month, Biofeedback for 15 sessions in IBS-C (3 months), Low FODMAP diet for 1 month, gluten free diet for 1 month, standard dietary advice from the NICE (UK) for 1 month, increase in physical activity.
• Patient with health insurance (AME excepted)
• Informed written consent
• For women with childbearing potential, efficient contraception for the duration of the participation to the study

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Exclusion Criteria

• Other chronic gastrointestinal disease (celiac disease, inflammatory bowel disease)
• participants if there is a reason to suspect an alternative diagnosis to the IBS complaints
• Surgical intervention in the gastrointestinal region except for appendectomy, hernia repair, cholecystectomy and hemorroidectomy
• Treatment preceding FMT with: antibiotics, antifungic or probiotics treatment < 4 weeks, or factors that may affect the composition of intestinal microbiota
• Abuse of alcohol or drugs
• Pregnancy or breastfeeding
• Participation in any other interventional study
• Patients under legal protection.
• Acute COVID-19 infection
• Presence of systemic disease, immune deficiency or treatment with immune-modulators
• Severe psychiatric disorder
• Participants who were assessed as likely to be noncompliant (ie, not adhering to the tasks they were to perform as participants)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Administration of the sham (PLACEBO)	Administration of the sham (PLACEBO)	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.
Administration of fecal microbiota transplantation ( FMT capsules)	Administration of fecal microbiota transplantation ( FMT capsules)	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.

Primary Outcome Measures

Name	Time	Method
Decrease in IBS severity at 12 weeks defined by the percentage of patients having at least a 75 points decrease in IBS-SSS.	At 12 weeks	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.

Secondary Outcome Measures

Name	Time	Method
FMT success	At 12 weeks	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).
Mean IBS-SSS (IBS severity), comparison between FMT and placebo at 12 and 24 weeks)	at week 12 and 24	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).
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.	V2: five weeks after inclusion. V3:Four weeks after V2	Patient's perception of FMT (questionnaire for correct assessment of FMT or placebo and FMT acceptability) (Annex D), secondary effects of FMT
Safety (Serious Adverse Events, Adverse Events) compared between groups.	through study completion, at 24 months	Safety (Serious Adverse Events, Adverse Events) compared between groups.
Intestinal microbiota composition at week 12 and 24 by 16s sequencing.	at week 12 and 24	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.
Decrease in IBS severity at 12 weeks defined by the percentage of patients having at least a 50 points decrease in IBS-SSS.	At 12 weeks	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)
Percentage of responders in the different subgroups IBS-D, IBS-C and IBS-M using the primary endpoint at week 12 and 24.	at week 12 and 24	IBS severity at 12 weeks by donors (one donor giving FMT to several patients)
Mean IBS-QoL score (IBS Quality of life) comparison between FMT and placebo at 12 and 24 weeks (Drossman et al. 2000)	at week 12 and 24	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).
Efficacy (decrease in IBS severity >75 points) at week 24 according to FMT success.	At 24 weeks	Efficacy (decrease in IBS severity \>75 points) according to FMT success.
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.	at week 12 and 24	Efficacy according to EMA (European Medical Agency) endpoint in IBS on composite criteria at 12 or 24 weeks

Trial Locations

Locations (1)

Gastro-enterology department, Avicenne Hospital; 🇫🇷 Bobigny, France