Allogeneic faecal microbiota, pooled for Severe irritable bowel syndrome (IBS)

Inclusion criteria

• {"criterion_text":"- Age >= 18 years and < 75 years\n- IBS defined according to Rome IV definition (IBS-C, IBS-D or IBS-M)\n- Severe disease (IBS-SSS >300) and refractory to at least two previous treatment strategies\n- Patient with health insurance (AME excepted)\n- Informed Written consent\n- For women with childbearing potential, efficient contraception for the duration of the participation to the study"}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- Decrease in IBS severity at 12 weeks is defined by the percentage of patients having at least a 75 points decrease in IBS-SSS","definition_or_measurement_approach":"Percentage of patients with at least a 75-point decrease in the IBS-SSS (IBS Severity Scoring System) at 12 weeks."}

Secondary endpoints

• {"endpoint_text":"- Decrease in IBS severity at 12 weeks defined by the percentage of patients having at least a 50 points decrease in IBS-SSS.","definition_or_measurement_approach":"Percentage of patients with at least a 50-point decrease in IBS-SSS at 12 weeks."}
• {"endpoint_text":"- FMT success : 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).","definition_or_measurement_approach":"Comparison using Sorensen similarity index between patient post-FMT vs donor and patient post-FMT vs patient pre-FMT; FMT success if Sorensen(patient after FMT vs donor) > Sorensen(patient after FMT vs patient before FMT) and Sorensen(patient after FMT vs donor) ≥ 0.6. Measurement by pyrosequencing (16S RNA)."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"16S sequencing at weeks 12 and 24; analysis using QIIME pipeline at all phylogenetic levels; diversity metrics: Shannon index, Simpson index, Chao1 index, and observed species; comparisons to baseline and donor microbiota."}
• {"endpoint_text":"- Efficacy at week 24 according to FMT success : decrease in IBS severity >75 points","definition_or_measurement_approach":"Percentage of patients with >75-point decrease in IBS-SSS at week 24, analysed according to FMT success status."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"EMA composite endpoint: simultaneous improvement of transit and abdominal pain for at least 50% of observation time, assessed at weeks 12 and 24."}
• {"endpoint_text":"- Percentage of responders in the different subgroups IBS-D, IBS-C and IBS-M using the primary endpoint at week 12 and 24.","definition_or_measurement_approach":"Proportion of responders (using the primary endpoint definition) within IBS subtypes (IBS-D, IBS-C, IBS-M) at weeks 12 and 24."}
• {"endpoint_text":"- Mean IBS-SSS (IBS severity), comparison between FMT and placebo at 12 and 24 weeks)","definition_or_measurement_approach":"Comparison of mean IBS-SSS scores between FMT and placebo groups at weeks 12 and 24."}
• {"endpoint_text":"- Mean IBS-QoL score (IBS Quality of life) comparison between FMT and placebo at 12 and 24 weeks (Drossman et al. 2000)","definition_or_measurement_approach":"Comparison of mean IBS-QoL scores between FMT and placebo at weeks 12 and 24, using the IBS-QoL instrument."}
• {"endpoint_text":"- Patient’s perception of FMT : 1/Questionnaire for correct assessment of FMT or placebo and FMT acceptability at V2 (FMT administration) (Annex D). 2/ Questionnaire for assessment of FMT secondary effects à V3 (Annex E)","definition_or_measurement_approach":"Patient questionnaires at V2 (acceptability/evaluation) and V3 (assessment of secondary effects) as specified in protocol annexes; descriptive analysis of responses."}
• {"endpoint_text":"- Safety (Serious Adverse Events, Adverse Events) compared between groups","definition_or_measurement_approach":"Comparison of incidence and nature of adverse events and serious adverse events between FMT and placebo groups."}

France

Earliest CTIS Part Ii Submission Date

18-10-2024

Latest Decision Or Authorization Date

21-05-2025

Processing Time Days

215

Number Of Sites

8

Number Of Participants

150

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France