Fecal Microbiota Transplantation for Chronic Pouchitis

Study Overview
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Brief Summary
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Patients with chronic pouchitis are treated with fecal transplant from several unrelated, healthy donors. The treatment consists of enemas of 100 mL fecal suspension, applied for 14 consecutive days.

Detailed Description
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Background: The surgical treatment of choice for the treatment of medically refractory ulcerative colitis (UC) is restorative ileal pouch-anal anastomosis (IPAA), in which the patient retains fecal continence following colonectomy, by subsequent anastomosis of the terminal ileum and the rectum. Up to 25% of patients with UC will undergo IPAA surgery. The most common complication following the procedure is inflammation of the pouch (pouchitis), which is seen in up to 50% of patients within the first five years of surgery. Of these patients, 10-20% will develop a chronic inflammatory condition. The clinical symptoms of pouchitis include diarrhea, rectal bleeding, stomach cramps, general malaise and reduced quality of life. Endoscopic findings include mucosal edema, granulations, and ulcerations with mucosal frailty. In most cases, a causative microorganism is not identified, although infection with Clostridium difficile or Cytomegalovirus (CMV) have been reported. The most common treatment of pouchitis is empiric antibiotics, usually quinolones and metronidazole, or a combination of both. Following complications, removal of the pouch can become a last resort, and chronic pouchitis is the leading indication for 10% of these operations. The composition of microbes in the gut is known to be a key factor in the homeostasis of the intestine, and plays a central role in the development of CIBD. Different single microorganisms have previously been suggested as playing an important role in this development, including: Mycobacterium avium, Escherichia coli and Clostridium difficile, that all have invasive capabilities. Several studies have investigated the connection between the composition of microbes in the gut and development of pouchitis finding an increasing evidence for a link between dysbiosis and pouchitis. Method: Patients with chronic pouchitis are treated with fecal transplants from unrelated, healthy donors. The fecal transplant is from several healthy donors. The treatments are applied as enemas of 100 ml suspension for 14 consecutive days. Prior to treatment, pouchitis activity is graded using the pouchitis disease activity index (PDAI) based on symptoms, endoscopic and histological criteria. Patients will also complete self-reported questionnaires regarding pouch function, quality of life and sexuality. Patients are evaluated using the PDAI score 30 days following treatment together with the self-reported questionnaires. Longterm follow up is evaluated up to 6 months following FMT. Screening of FMT donors: Questionaire regarding possible contagious infectious diseases, followed by interview with principal investigator. Blood test for: inflammatory parameters: CRP, leucocyte count, HIV 1+2 antigen, Hepatitis A, B and C, CMV, EBV and HbA1c Fecal samples: Calprotectin Pathogenic bacteria (Salmonella, Campylobacter, Yersinia, Shigella), Vibrio, toxin-producing E. coli. Parasites, giardia spp. and cryptosporidium spp. Adenovirus, enterovirus, parechovirus Clostridium difficile Vancomycin-resistent Enterococcus faecalis and Enterococcus faecium, carbapenemase-producing enterobacteria and ESBL-producing E.coli. FMT donor exclusion criteria are: Age <20 or >65 BMI <18.5 or > 28.0 kg/m2 Known chronic inflammatory bowel disease, celiac disease, rheumatoid arthritis or other autoimmune disease, sclerosis, psoriasis, previous extensive bowel surgery In the previous 6 months: Diarrhea > 3 days in one week or bloody stools Treatment with antibiotics Risk of sexually transmitted disease, tattoos, piercings, travel to areas with high endemic transmission of infectious diseases or resistants microbes.

Official Title
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Fecal Microbiota Transplantation for the Treatment of Chronic Pouchitis

Conditions
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Pouchitis, Ulcerative Colitis

Intervention / Treatment
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* Other: Donor FMT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: minimum 18 years old, pouch > 1 year at least three pouchitis events in the past year antibiotic treatment for pouchitis at least one time in the past year Exclusion Criteria: immunosuppression, pregnancy, detection of specific pathogens in stool

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donor FMT<br>Fecal transplant from unrelated, healthy volunteers | Other: Donor FMT<br>* Fecal transplant from unrelated, healthy donors using enemas<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cure 30 days following FMT treatment | PDAI < 7 | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of the microbiota | Changes in diversity of gut microbiota after FMT assessed by Shannon index | 30 days | 
| Clinical response 30 days after FMT treatment | Decrease from baseline PDAI > 2 points | 30 days | 
| Histological remission following PDAI | Remission of microscopic inflammation | 30 days | 
| Improvement of pouch function | Improvement of the self-reported questionnaire | 30 days | 
| Improvement of quality of life | Improvement of the self-reported questionnaire | 30 days | 
| Improvement of sexuality | Improvement of the self-reported questionnaire | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative Colitis, Inflammatory bowel disease, Pouchitis, Fecal microbiota transplant, Fecal microbiota treatment