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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-003433-41 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Administration of the sham (PLACEBO) | Placebo Comparator | 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. |
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| Administration of fecal microbiota transplantation ( FMT capsules) | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Administration of fecal microbiota transplantation ( FMT capsules) | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | At 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | At 12 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jean Marc SABATE, Pr | Contact | 01 48 95 54 34 | jean-marc.sabate@aphp.fr | |
| Nacira DARGHAL, PhD | Contact | 01 48 95 74 73 | nacira.darghal@aphp.fr |
| Name | Affiliation | Role |
|---|---|---|
| Jean Marc SABATE, Pr | Assistance Publique - Hôpitaux de Paris | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Gastro-enterology department, Avicenne Hospital | Bobigny | 93000 | France |
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| ID | Term |
|---|---|
| D043183 | Irritable Bowel Syndrome |
| ID | Term |
|---|---|
| D003109 | Colonic Diseases, Functional |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
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| ID | Term |
|---|---|
| D000069467 | Fecal Microbiota Transplantation |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
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| Administration of the sham (PLACEBO) | Drug | 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. |
|
| 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). | 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. | 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. | 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 | 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) | 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). | 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). | 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 | 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. | through study completion, at 24 months |
| D004066 | Digestive System Diseases |