## Protocol Section
### Identification Module
**NCT ID:** NCT06433180

**Acronym:** ICEBOAT

**Brief Title:** 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).

#### Organization Study ID Info
**ID:** APHP180583
#### Organization
**Class:** OTHER
**Full Name:** Assistance Publique - Hôpitaux de Paris
#### Secondary ID Infos
**ID:** 2019-003433-41
**Type:** EUDRACT_NUMBER
### Status Module
#### Completion Date
**Date:** 2029-07-15

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-29

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-26

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2028-07-15

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-04

#### Study First Post Date
**Date:** 2024-05-29
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-13
**Study First Submit QC Date:** 2024-05-26
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Assistance Publique - Hôpitaux de Paris

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**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.

### Conditions Module

**Conditions:**

- Irritable Bowel Syndrome

**Keywords:**

- fecal microbiota transplantation

- irritable bowel syndrome

- frozen capsule

- Rome IV

- IBS-SSS

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 150

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Drug: Administration of the sham (PLACEBO)

**Label:** Administration of the sham (PLACEBO)

**Type:** PLACEBO_COMPARATOR

#### Arm Group 2

**Description:** 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.

**Intervention Names:**

- Drug: Administration of fecal microbiota transplantation ( FMT capsules)

**Label:** Administration of fecal microbiota transplantation ( FMT capsules)

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Administration of fecal microbiota transplantation ( FMT capsules)

**Description:** 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.

**Name:** Administration of fecal microbiota transplantation ( FMT capsules)

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Administration of the sham (PLACEBO)

**Description:** 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.

**Name:** Administration of the sham (PLACEBO)

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** Decrease in IBS severity at 12 weeks defined by the percentage of patients having at least a 75 points decrease in IBS-SSS.

**Time Frame:** At 12 weeks

#### Secondary Outcomes

**Description:** 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)

**Measure:** Decrease in IBS severity at 12 weeks defined by the percentage of patients having at least a 50 points decrease in IBS-SSS.

**Time Frame:** At 12 weeks

**Description:** 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).

**Measure:** FMT success

**Time Frame:** At 12 weeks

**Description:** 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.

**Measure:** Intestinal microbiota composition at week 12 and 24 by 16s sequencing.

**Time Frame:** at week 12 and 24

**Description:** Efficacy (decrease in IBS severity \>75 points) according to FMT success.

**Measure:** Efficacy (decrease in IBS severity >75 points) at week 24 according to FMT success.

**Time Frame:** At 24 weeks

**Description:** Efficacy according to EMA (European Medical Agency) endpoint in IBS on composite criteria at 12 or 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.

**Time Frame:** at week 12 and 24

**Description:** IBS severity at 12 weeks by donors (one donor giving FMT to several patients)

**Measure:** Percentage of responders in the different subgroups IBS-D, IBS-C and IBS-M using the primary endpoint at week 12 and 24.

**Time Frame:** at week 12 and 24

**Description:** 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).

**Measure:** Mean IBS-SSS (IBS severity), comparison between FMT and placebo at 12 and 24 weeks)

**Time Frame:** at week 12 and 24

**Description:** 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).

**Measure:** Mean IBS-QoL score (IBS Quality of life) comparison between FMT and placebo at 12 and 24 weeks (Drossman et al. 2000)

**Time Frame:** at week 12 and 24

**Description:** Patient's perception of FMT (questionnaire for correct assessment of FMT or placebo and FMT acceptability) (Annex D), secondary effects of FMT

**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.

**Time Frame:** V2: five weeks after inclusion. V3:Four weeks after V2

**Description:** Safety (Serious Adverse Events, Adverse Events) compared between groups.

**Measure:** Safety (Serious Adverse Events, Adverse Events) compared between groups.

**Time Frame:** through study completion, at 24 months

### Eligibility Module

**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)

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** jean-marc.sabate@aphp.fr

**Name:** Jean Marc SABATE, Pr

**Phone:** 01 48 95 54 34

**Role:** CONTACT

**Contact 2:**

**Email:** nacira.darghal@aphp.fr

**Name:** Nacira DARGHAL, PhD

**Phone:** 01 48 95 74 73

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Bobigny

**Contacts:**

***Contact 1:***

- **Email:** jean-marc.sabate@aphp.fr

- **Name:** Jean MARC SABATE, Pr

- **Phone:** 01 48 95 54 34

- **Role:** CONTACT

***Contact 2:***

- **Email:** nacira.darghal@aphp.fr

- **Name:** Nacira DARGHAL, PhD

- **Phone:** 01 48 95 74 73

- **Role:** CONTACT

**Country:** France

**Facility:** Gastro-enterology department, Avicenne Hospital

**Zip:** 93000

#### Overall Officials

**Official 1:**

**Affiliation:** Assistance Publique - Hôpitaux de Paris

**Name:** Jean Marc SABATE, Pr

**Role:** STUDY_DIRECTOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004194

- Term: Disease

- ID: D000010335

- Term: Pathologic Processes

- ID: D000003109

- Term: Colonic Diseases, Functional

- ID: D000003108

- Term: Colonic Diseases

- ID: D000007410

- Term: Intestinal Diseases

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000004066

- Term: Digestive System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC06

- Name: Digestive System Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: HIGH

- As Found: Syndrome

- ID: M25118

- Name: Irritable Bowel Syndrome

- Relevance: HIGH

- As Found: Irritable Bowel Syndrome

- ID: M6336

- Name: Colonic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6337

- Name: Colonic Diseases, Functional

- Relevance: LOW

- As Found: Unknown

- ID: M10444

- Name: Intestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000043183

- Term: Irritable Bowel Syndrome

- ID: D000013577

- Term: Syndrome

### Intervention Browse Module - Browse Branches

- Abbrev: PhSol

- Name: Pharmaceutical Solutions

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: HB

- Name: Herbal and Botanical

### Intervention Browse Module - Browse Leaves

- ID: M21860

- Name: Pharmaceutical Solutions

- Relevance: LOW

- As Found: Unknown

- ID: T120

- Name: Cola

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
