Transplantation of Faeces in Ulcerative Colitis; Restoring Nature's Homeostasis (TURN)

Transplantation of Faeces in Ulcerative Colitis; Restoring Nature's Homeostasis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of the colon. Complaints such as abdominal pain, cramps and bloody diarrhoea usually start in early adulthood and lead to life-long substantial morbidity. There is no medical treatment available that meets the desired criteria of high efficacy versus low adverse effects. The current prevailing hypothesis regarding the cause of UC states that the pathogenesis involves an inappropriate and ongoing activation of the mucosal immune system driven by the intestinal microbiota in a genetically predisposed individual. Systematic investigation into the effect of correcting the dysbiosis in ulcerative colitis patients has never been performed. The most radical way to restore the presumably disturbed natural homeostasis in UC is to perform faecal transplantation from a healthy donor. In this trial the potential beneficial effects of restoring microbial homeostasis by faecal transplantation through a duodenal tube will be studied in a phase II randomised placebo controlled design.

Endpoints are clinical remission and reduction of endoscopic inflammation after 12 weeks (primary), as well as time to recurrence, intra individual changes in faecal samples and mucosal biopsies. Follow up is 12 months.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Other: treatment with faecal transplantation (donor faeces); Other: treatment with faecal transplantation (own faeces)

Detailed Description

treatment with faecal transplantation from a healthy donor in active ulcerative colitis patients. In this trial the potential beneficial effects of restoring microbial homeostasis by faecal transplantation through a duodenal tube will be studied in a phase II randomised placebo controlled design.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1100DD
    • Academic_Medical_Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18
• Ability to give informed consent
• Established ulcerative colitis with known involvement of the left colon according to the Lennard-Jones criteria
• SCCAI of 4 > < 11
• Endoscopic Mayo score of > 1
• Stable dose of thiopurines in preceding 8 weeks
• Stable dose of corticosteroids and 5-ASA in preceding 2 weeks

Exclusion Criteria:

• Condition leading to profound immunosuppression
• Anti-TNF treatment in preceding 2 months
• Cyclosporine treatment in preceding 4 weeks
• Use of Methotrexate in preceding 2 months
• Prednisolone dose > 10 mg
• Life expectancy < 12 months
• Use of systemic antibiotics in preceding 6 weeks
• Use of probiotic treatment in preceding 6 weeks
• Positive stool cultures for common enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, enteropathogenic e coli)
• Positive faecal PCR-test (positive PCR means: > 1 of the following viruses is present) for: Rotavirus, Norovirus, Enterovirus, Parechovirus Sapovirus, Adenovirus 40/41/52. Astrovirus.
• Pregnancy or women who give breastfeeding
• Vasopressive medication, icu stay

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: faecal transplantation; donor faeces; 2 times treatment with faecal transplantation: faeces from a healthy donor processed for duodenal tube infusion. after bowel lavage with macrogol.	Other: treatment with faecal transplantation (donor faeces); faecal transplantation
PLACEBO_COMPARATOR: faecal transplantation; placebo; 2 times treatment with (own) faecal transplantation: faeces from the patient processed for duodenal tube infusion. after bowel lavage with macrogol.	Other: treatment with faecal transplantation (own faeces); faecal transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
co-primary endpoint of clinical remission, as well as reduction of Mayo endoscopic inflammation score	clinical remission = questionnaire: SCCAI 2 or lower; reduction of Mayo endoscopic inflammation score= decrement of 1 or more as assessed by sigmoidoscopy	at 12 weeks after treatment.

Secondary Outcome Measures

Outcome Measure	Time Frame
Simple clinical colitis activity index (SCCAI) score reduction	time: 6 weeks after treatment
Frequency of bowel movements	start at baseline up to 6 weeks after treatment
Time to recurrence	from timepoint 12 weeks after treatment up to 12 months

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: C Ponsioen, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

General Publications

• Rossen NG, Fuentes S, van der Spek MJ, Tijssen JG, Hartman JH, Duflou A, Lowenberg M, van den Brink GR, Mathus-Vliegen EM, de Vos WM, Zoetendal EG, D'Haens GR, Ponsioen CY. Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. Gastroenterology. 2015 Jul;149(1):110-118.e4. doi: 10.1053/j.gastro.2015.03.045. Epub 2015 Mar 30.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (ACTUAL): August 1, 2014
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: July 18, 2012
• First Submitted That Met QC Criteria: July 25, 2012
• First Posted (ESTIMATE): July 26, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): December 30, 2014
• Last Update Submitted That Met QC Criteria: December 28, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: ulcerative colitis; inflammatory bowel disease; faecal transplantation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: METC 2011_005