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

Pouchitis Clinical Trial

— POCA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03524352
• Other study ID #: RC17_0021
• Status: Recruiting
• Phase: Phase 3
• Start date: March 12, 2020
• Est. completion date: May 12, 2028

Study information

• Verified date: June 2023
• Source: Nantes University Hospital
• Contact: Trang POISSON
• Phone: +33 2 40 08 75 59
• Email: caroline.trang[@]chu-nantes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: May 12, 2028
• Est. primary completion date: May 12, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

4.2. INCLUSION CRITERIA

Subjects must satisfy the following criteria to be enrolled in the study:

1. Male or female = 18 years at the time of signing the informed consent form (ICF).

2. Subject must understand and voluntarily sign an ICF prior to conduct the study related assessments/procedure.

3. Willing and able to adhere to the study visit scheduled and other protocol requirements.

4. Subjects must have been operated with ileal pouch anal anastomosis (IPAA) with a duration of at least 6 month prior the screening visit.

5. 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).

6. Subject must be in remission with a Pouchitis Disease Activity Index (PDAI) < 7 at the screening

7. Subject must affiliation with social security system or beneficiary from such system

8. 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:

1. Crohn disease or indeterminate colitis

2. Anastomotic stenosis

3. Subject with prior treatment by probiotic within 3 month prior to the transplantation visit

4. Subject with prior treatment by corticosteroids within 6 weeks prior to the transplantation visit

5. Subject with prior treatment by immunosuppressors within 3 month prior to the transplantation visit

6. Prior treatment with a biologic within 3 month prior the transplantation visit

7. Documented active infection of any kind in the last 6 months likely to require anti-infective treatment during the next months

8. Absolute neutrophil count (ANC) < 1.5 x 109 /L (1,500 mm3)

9. Infection with chronic HIV

10. Pregnant female or breastfeeding

11. Chronic medical or psychiatric disease that may interfere with subject's ability to comply with study procedures

12. Administration of investigational drug within 3 months prior to planned FMT

13. Adults under guardianship, Safeguard justice or trusteeship

14. Subject with difficulty in follow-up (vacation, job transfer, geographical distance, lack of motivation).

15. Patients with contraindication to colonoscopy or anesthesia (if necessary)

Related Conditions & MeSH terms

• Pouchitis

Intervention

Other:
• fecal microbiota
fecal microbiota in suspension
• Placebo
sterile saline

Locations

Country	Name	City	State
France	CHU Angers	Angers
France	CHU Estaing	Clermont-Ferrand
France	Hopital Beaujon, Clichy	Clichy
France	CHU Henry Mondor	Créteil
France	CHU Claude Huriez	Lille
France	CHU Lyon Sud	Lyon
France	CHU of Nantes	Nantes
France	CHU de l'Archet 2	Nice
France	Hopital Saint Antoine	Paris
France	Groupe Hospitalier Sud- Hopital Haut-lévêque	Pessac
France	CHU Pontchaillou	Rennes
France	CHU Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

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