Clinical trial NCT06433180: Study of Fecal Microbiota Transplantation (FMT) in Severe IBS Patients
Official title: A Prospective, Multi-center, Double Blind Randomized Trial of Fecal Microbiota Transplantation (FMT) Delivered by Capsule Versus Placebo in Severe Irritable Bowel Syndrome (IBS).
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Irritable Bowel Syndrome
Keywords: fecal microbiota transplantation
irritable bowel syndrome
frozen capsule
Rome IV
IBS-SSS
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-05-29
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

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)

Primary outcomes:
measure: Decrease in IBS severity at 12 weeks defined by the percentage of patients having at least a 75 points decrease in IBS-SSS.
timeFrame: At 12 weeks
Secondary outcomes:
measure: Decrease in IBS severity at 12 weeks defined by the percentage of patients having at least a 50 points decrease in IBS-SSS.
timeFrame: At 12 weeks
measure: FMT success
timeFrame: At 12 weeks
measure: Intestinal microbiota composition at week 12 and 24 by 16s sequencing.
timeFrame: at week 12 and 24
measure: Efficacy (decrease in IBS severity >75 points) at week 24 according to FMT success.
timeFrame: At 24 weeks
measure: 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.
timeFrame: at week 12 and 24
measure: Percentage of responders in the different subgroups IBS-D, IBS-C and IBS-M using the primary endpoint at week 12 and 24.
timeFrame: at week 12 and 24
measure: Mean IBS-SSS (IBS severity), comparison between FMT and placebo at 12 and 24 weeks)
timeFrame: at week 12 and 24
measure: Mean IBS-QoL score (IBS Quality of life) comparison between FMT and placebo at 12 and 24 weeks (Drossman et al. 2000)
timeFrame: at week 12 and 24
measure: 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.
timeFrame: V2: five weeks after inclusion. V3:Four weeks after V2
measure: Safety (Serious Adverse Events, Adverse Events) compared between groups.
timeFrame: through study completion, at 24 months
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Gastro-enterology department, Avicenne Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Jean Marc SABATE, Pr
role: STUDY_DIRECTOR
References: