Fecal Microbiota Transplantation for Chronic Pouchitis

NCT ID: NCT03538366

Last Updated: 2019-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-15

Study Completion Date

2019-05-01

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:

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.

Conditions

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Ulcerative Colitis Pouchitis

Keywords

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Donor FMT

Fecal transplant from unrelated, healthy volunteers

Group Type EXPERIMENTAL

Donor FMT

Intervention Type OTHER

Fecal transplant from unrelated, healthy donors using enemas

Interventions

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Donor FMT

Fecal transplant from unrelated, healthy donors using enemas

Intervention Type OTHER

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Aalborg University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery

MD, DMSc, Professor of Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ole Thorlacius-Ussing, Professor

Role: STUDY_DIRECTOR

Aalborg University Hospital, Aalborg University

Locations

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Research Unit, Department of Gastrointestinal Surgery

Aalborg, , Denmark

Site Status

Countries

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Denmark

References

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Becker JM. Surgical therapy for ulcerative colitis and Crohn's disease. Gastroenterol Clin North Am. 1999 Jun;28(2):371-90, viii-ix. doi: 10.1016/s0889-8553(05)70061-3.

Reference Type BACKGROUND
PMID: 10372273 (View on PubMed)

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. doi: 10.1097/01.sla.0000098115.90865.16.

Reference Type BACKGROUND
PMID: 14703744 (View on PubMed)

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. doi: 10.1007/s10350-006-0608-0.

Reference Type BACKGROUND
PMID: 16830218 (View on PubMed)

Sandborn WJ. Pouchitis following ileal pouch-anal anastomosis: definition, pathogenesis, and treatment. Gastroenterology. 1994 Dec;107(6):1856-60. doi: 10.1016/0016-5085(94)90832-x. No abstract available.

Reference Type BACKGROUND
PMID: 7958702 (View on PubMed)

Shen B. Diagnosis and treatment of patients with pouchitis. Drugs. 2003;63(5):453-61. doi: 10.2165/00003495-200363050-00002.

Reference Type BACKGROUND
PMID: 12600225 (View on PubMed)

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. doi: 10.1097/00054725-200111000-00004.

Reference Type BACKGROUND
PMID: 11720319 (View on PubMed)

Sandborn WJ, Pardi DS. Clinical management of pouchitis. Gastroenterology. 2004 Dec;127(6):1809-14. doi: 10.1053/j.gastro.2004.10.011. No abstract available.

Reference Type BACKGROUND
PMID: 15578518 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21407187 (View on PubMed)

Tulchinsky H, Hawley PR, Nicholls J. Long-term failure after restorative proctocolectomy for ulcerative colitis. Ann Surg. 2003 Aug;238(2):229-34. doi: 10.1097/01.sla.0000082121.84763.4c.

Reference Type BACKGROUND
PMID: 12894016 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25110406 (View on PubMed)

Other Identifiers

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FMT and Pouchitis

Identifier Type: -

Identifier Source: org_study_id