A Pilot Study of FMT on CD Patients With AIEC

Study Overview
=================
Brief Summary
-----------------
The goal of this pilot study is to test whether Fecal Microbiota Transplant (FMT) would be an effective antibacterial treatment for managing Adherent-invasive Escherichia coli (AIEC) colonization in Crohn's disease (CD) patients. It aims to assess the safety of FMT in patients with clinically inactive or mild to moderate CD and to determine the presence of AIEC before and after FMT. Participants will receive FMT via colonoscopy and have a follow-up colonoscopy at the end of the study.

Detailed Description
-----------------
Experimental and observational data suggest that intestinal inflammation in Crohn's Disease (CD) arises from abnormal immune response to intestinal microbiota in genetically susceptible individuals. Genes that regulate innate immune response, intestinal barrier function and bacteria killing of intracellular pathogens have been associated with an increased risk for developing CD in Caucasian populations. The search for specific pathogens in CD has identified in the intestinal mucosa of patients several candidates. One with much supporting evidence is the adherent invasive Escherichia coli (AIEC). Since its discovery in 1998, several groups have reported a higher prevalence of AIEC in CD patients compared to healthy subjects and confirmed their pro-inflammatory potential. A growing body of work indicates that different host environments can select such AIEC pathobiont. AIEC colonization in mice leads to strong inflammatory responses in the gut suggesting that AIEC could play a role in CD immunopathogenesis. Faecal microbiota transplantation (FMT) represents a clinically feasible way to restore the gut microbial ecology and has proven to be a breakthrough for the treatment of recurrent Clostridium difficile infection. Clinical trials are being conducted to evaluate its use for other conditions including inflammatory bowel disease, irritable bowel syndrome, diabetes mellitus, non-alcoholic steatohepatitis and hepatic encephalopathy. Efficacy of FMT on CD endoscopic lesions and AIEC colonization remains to be demonstrated.

Official Title
-----------------
A Pilot Study of Fecal Microbiota Transplant (FMT) and Its Effects in Patients With Crohn's Disease With Moderate-to-High Risk of Colonization of Adherent-Invasive E. Coli (AIEC)

Conditions
-----------------
Crohn Disease

Intervention / Treatment
-----------------
* Procedure: Fecal Microbiota Transplantation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: >18 years of age; Patients with CD history ≥ 3-month duration; Patients with no or mild-to-moderate symptoms defined as Harvey Bradshaw Index (HBI) < 16 ; Patients with positive total E.coli antibodies (AEcAb) Exclusion Criteria: Pregnancy; New biological treatment or steroids use within 4 weeks; Current Colorectal tumor; Active gastrointestinal bleeding; Having ulcerative colitis; Having colectomy or partial colectomy (less than ileo-transverse colonic anastomosis); Having colonic or small bowel stoma; Active perianal lesions; Receiving antibiotics within 4 weeks; Presenting psychological or linguistic incapability to sign the informed consent
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All recruited patients will receive FMT.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fecal Microbiota Transplantation<br>Recruited patients will receive Fecal Microbiota Transplantation | Procedure: Fecal Microbiota Transplantation<br>* FMT at Week 0<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Event | Occurrence of any adverse events | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in AIEC colonization | Presence of mucosa-associated AIEC before and after receiving FMT | Week 12 | 
| Change in inflammatory biomarker Erythrocyte sedimentation rate (ESR) |  | Week 12 | 
| Change in inflammatory biomarker C-reactive protein (CRP) |  | Week 12 | 
| Change in fecal microbiota | Fecal microbiota, including diversity, composition and functional capacity will be measured before and after receiving FMT | Week 12 | 
| Disease Severity | Harvey Bradshaw Index score will be used to measure disease severity where scores higher than 16 indicate disease activity is severe | Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fecal Microbiota Transplant, Adherent-invasive Escherichia coli