Fecal Microbiota Transplantation for Chronic Pouchitis

• ClinicalTrials.gov Identifier: NCT03538366
• Recruitment Status: Completed
• First Posted: May 29, 2018
• Last Update Posted: December 19, 2019
• Sponsor: Aalborg University Hospital
• Information provided by (Responsible Party): Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery, Aalborg University Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Ulcerative Colitis; Pouchitis	Other: Donor FMT	Not Applicable

Detailed Description:

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:

1. Questionaire regarding possible contagious infectious diseases, followed by interview with principal investigator.
2. Blood test for: inflammatory parameters: CRP, leucocyte count, HIV 1+2 antigen, Hepatitis A, B and C, CMV, EBV and HbA1c

3. Fecal samples:

   1. Calprotectin
   2. Pathogenic bacteria (Salmonella, Campylobacter, Yersinia, Shigella), Vibrio, toxin-producing E. coli.
   3. Parasites, giardia spp. and cryptosporidium spp.
   4. Adenovirus, enterovirus, parechovirus
   5. Clostridium difficile
   6. 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Fecal Microbiota Transplantation for the Treatment of Chronic Pouchitis
• Actual Study Start Date: May 15, 2018
• Actual Primary Completion Date: May 1, 2019
• Actual Study Completion Date: May 1, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Donor FMT; Fecal transplant from unrelated, healthy volunteers	Other: Donor FMT; Fecal transplant from unrelated, healthy donors using enemas

Outcome Measures

Primary Outcome Measures :

1. Cure 30 days following FMT treatment [ Time Frame: 30 days ]
   PDAI < 7

Secondary Outcome Measures :

1. Changes of the microbiota [ Time Frame: 30 days ]
   Changes in diversity of gut microbiota after FMT assessed by Shannon index
2. Clinical response 30 days after FMT treatment [ Time Frame: 30 days ]
   Decrease from baseline PDAI > 2 points
3. Histological remission following PDAI [ Time Frame: 30 days ]
   Remission of microscopic inflammation
4. Improvement of pouch function [ Time Frame: 30 days ]
   Improvement of the self-reported questionnaire
5. Improvement of quality of life [ Time Frame: 30 days ]
   Improvement of the self-reported questionnaire
6. Improvement of sexuality [ Time Frame: 30 days ]
   Improvement of the self-reported questionnaire

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Denmark

Research Unit, Department of Gastrointestinal Surgery

Aalborg, Denmark, 9000

Sponsors and Collaborators

Aalborg University Hospital

Investigators

• Study Director: Ole Thorlacius-Ussing, Professor; Aalborg University Hospital, Aalborg University

More Information

Publications:

Becker JM. Surgical therapy for ulcerative colitis and Crohn's disease. Gastroenterol Clin North Am. 1999 Jun;28(2):371-90, viii-ix. Review.

Onaitis MW, Mantyh C. Ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous polyposis: historical development and current status. Ann Surg. 2003 Dec;238(6 Suppl):S42-8. Review.

Lovegrove RE, Tilney HS, Heriot AG, von Roon AC, Athanasiou T, Church J, Fazio VW, Tekkis PP. A comparison of adverse events and functional outcomes after restorative proctocolectomy for familial adenomatous polyposis and ulcerative colitis. Dis Colon Rectum. 2006 Sep;49(9):1293-306.

Sandborn WJ. Pouchitis following ileal pouch-anal anastomosis: definition, pathogenesis, and treatment. Gastroenterology. 1994 Dec;107(6):1856-60. Review.

Shen B. Diagnosis and treatment of patients with pouchitis. Drugs. 2003;63(5):453-61. Review.

Shen B, Achkar JP, Lashner BA, Ormsby AH, Remzi FH, Brzezinski A, Bevins CL, Bambrick ML, Seidner DL, Fazio VW. A randomized clinical trial of ciprofloxacin and metronidazole to treat acute pouchitis. Inflamm Bowel Dis. 2001 Nov;7(4):301-5.

Sandborn WJ, Pardi DS. Clinical management of pouchitis. Gastroenterology. 2004 Dec;127(6):1809-14.

Khan KJ, Ullman TA, Ford AC, Abreu MT, Abadir A, Marshall JK, Talley NJ, Moayyedi P. Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis. Am J Gastroenterol. 2011 Apr;106(4):661-73. doi: 10.1038/ajg.2011.72. Epub 2011 Mar 15. Review. Erratum in: Am J Gastroenterol. 2011 May;106(5):1014. Abadir, A [corrected to Abadir, Amir].

Tulchinsky H, Hawley PR, Nicholls J. Long-term failure after restorative proctocolectomy for ulcerative colitis. Ann Surg. 2003 Aug;238(2):229-34.

Angriman I, Scarpa M, Castagliuolo I. Relationship between pouch microbiota and pouchitis following restorative proctocolectomy for ulcerative colitis. World J Gastroenterol. 2014 Aug 7;20(29):9665-74. doi: 10.3748/wjg.v20.i29.9665. Review.

• Responsible Party: Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery, MD, DMSc, Professor of Surgery, Aalborg University Hospital
• ClinicalTrials.gov Identifier: NCT03538366
• Other Study ID Numbers: FMT and Pouchitis
• First Posted: May 29, 2018
• Last Update Posted: December 19, 2019
• Last Verified: December 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery, Aalborg University Hospital:

Ulcerative Colitis; Inflammatory bowel disease; Pouchitis; Fecal microbiota transplant; Fecal microbiota treatment

Additional relevant MeSH terms:

Colitis; Colitis, Ulcerative; Pouchitis; Ulcer; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Pathologic Processes; Inflammatory Bowel Diseases; Ileitis; Enteritis; Ileal Diseases