the Prophylaxis of Recurrent Pouchitis After Fecal Microbiota Transplant in UC With Ileo-anal Anastomosis

Study Overview
=================
Brief Summary
-----------------
Ulcerative colitis (UC) is a chronic inflammatory digestive (IBD) disease medically treated with corticosteroids, aminosalicylates, immunomodulators, and biologics. Almost one third of UC patients will require surgical interventions because of fulminant colitis, dysplasia, cancer, or medical refractory diseases. Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the current standard surgical intervention. Anastomotic leak, pouch failure, pelvic sepsis, and pouch ischemia can occur after the procedure, but the most common long-term complication is pouchitis, an idiopathic inflammatory condition involving the ileal reservoir. Symptoms of pouchitis are increased stool frequency, urgency, incontinence, bloody stools, abdominal or pelvic discomfort, fatigue, malaise, and fever. The prevalence of pouchitis ranges from 23 to 46 %, with an annual incidence up to 40 %. Though the majority of initial cases of pouchitis are easily managed with a short course of antibiotics, in about 5 to 15 % of cases, inflammation of the pouch becomes chronic with very few treatments available. Fecal microbiota transplantation (FMT) is a novel therapy to transfer normal intestinal flora from a healthy donor to a patient with a medical condition potentially caused by disrupted homeostasis of intestinal microbiota or dysbiosis. FMT has been widely used in refractory Clostridium difficile infection (CDI) and recently it has gained popularity for treatment of inflammatory bowel disease (IBD). Previous studies suggested that manipulating the composition of intestinal flora through antibiotics, probiotics, and prebiotic achieved significant results for treating acute episodes of UC-associated pouchitis. However, currently there is no established effective treatment for chronic antibiotic dependent pouchitis. Our project aims to evaluate the delay of relapse in chronic recurrent pouchitis after FMT versus sham transplantation.

Official Title
-----------------
Prospective Multicenter Randomized Controlled Double-blind Label Study of the Prophylaxis of Recurrent Pouchitis After Fecal Microbiota Transplant in UC With Ileo-anal Anastomosis

Conditions
-----------------
Pouchitis

Intervention / Treatment
-----------------
* Other: fecal microbiota
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
4.2. INCLUSION CRITERIA Subjects must satisfy the following criteria to be enrolled in the study: Male or female ≥ 18 years at the time of signing the informed consent form (ICF). Subject must understand and voluntarily sign an ICF prior to conduct the study related assessments/procedure. Willing and able to adhere to the study visit scheduled and other protocol requirements. Subjects must have been operated with ileal pouch anal anastomosis (IPAA) with a duration of at least 6 month prior the screening visit. Subject must have a diagnosis of recurrent pouchitis defined as at least 2 episodes in the last year or relapsing immediately after a reasonable response to antibiotherapy (the antifungal medication is allowed until the day before transplantation). Subject must be in remission with a Pouchitis Disease Activity Index (PDAI) < 7 at the screening Subject must affiliation with social security system or beneficiary from such system Female of childbearing potential must have a negative pregnancy test at screening and must agree to practice effective methods of contraception 4.3. NON-INCLUSION CRITERIA Subjects who meet any of the following non inclusion criteria could not be enrolled in this study: Crohn disease or indeterminate colitis Anastomotic stenosis Subject with prior treatment by probiotic within 3 month prior to the transplantation visit Subject with prior treatment by corticosteroids within 6 weeks prior to the transplantation visit Subject with prior treatment by immunosuppressors within 3 month prior to the transplantation visit Prior treatment with a biologic within 3 month prior the transplantation visit Documented active infection of any kind in the last 6 months likely to require anti-infective treatment during the next months Absolute neutrophil count (ANC) < 1.5 x 109 /L (1,500 mm3) Infection with chronic HIV Pregnant female or breastfeeding Chronic medical or psychiatric disease that may interfere with subject's ability to comply with study procedures Administration of investigational drug within 3 months prior to planned FMT Adults under guardianship, Safeguard justice or trusteeship Subject with difficulty in follow-up (vacation, job transfer, geographical distance, lack of motivation). Patients with contraindication to colonoscopy or anesthesia (if necessary)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: fecal microbiota<br> | Other: fecal microbiota<br>* fecal microbiota in suspension<br>|
| Placebo Comparator: placebo<br> | Other: Placebo<br>* sterile saline<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days between the date of transplantation and the date of relapse according to physiological and endoscopic parameter (pochitis disease activity index) |  | 106 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of relapse rate according to physiological and endoscopic parameter (pochitis disease activity index) |  | 24 weeks | 
| Number of relapse rate according to pochitis disease activity index (physiological and endoscopic parameter) |  | 52 weeks | 
| Number of days within the transplantation and the instauration of an antibiotherapy or alternative treatment |  | 52 weeks | 
| Number of adverse events |  | 104 weeks | 
| Number of fecal microbiota engraftment by 16S sequencing |  | 8 weeks | 
| Number of evolution of health-related to disability according to physiological and endoscopic parameter (pochitis disease activity index) |  | weeks -5 | 
| Number of evolution of health-related to disability according to physiological and endoscopic parameter (pochitis disease activity index) |  | 0 week | 
| Number of evolution of health-related to disability according to physiological and endoscopic parameter (pochitis disease activity index) |  | 8 weeks | 
| Number of evolution of health-related to disability according to physiological and endoscopic parameter (pochitis disease activity index) |  | 24 weeks | 
| Number of evolution of health-related to disability according to physiological and endoscopic parameter (pochitis disease activity index) |  | 52 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent pouchitis, fecal microbiota transplant