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

• ClinicalTrials.gov Identifier: NCT01650038
• Recruitment Status: Completed
• First Posted: July 26, 2012
• Last Update Posted: December 30, 2014
• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Information provided by (Responsible Party): C.Y. Ponsioen, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Tracking Information

• First Submitted Date: July 18, 2012
• First Posted Date: July 26, 2012
• Last Update Posted Date: December 30, 2014
• Study Start Date: May 2011
• Actual Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 6, 2012)

co-primary endpoint of clinical remission, as well as reduction of Mayo endoscopic inflammation score [ Time Frame: at 12 weeks after treatment. ]

• clinical remission = questionnaire: SCCAI 2 or lower
• reduction of Mayo endoscopic inflammation score= decrement of 1 or more as assessed by sigmoidoscopy

• Original Primary Outcome Measures (submitted: July 25, 2012): co-primary endpoint of clinical remission, as well as reduction of Mayo endoscopic inflammation score [ Time Frame: at 12 weeks after treatment. ]

Current Secondary Outcome Measures (submitted: July 25, 2012)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Transplantation of Faeces in Ulcerative Colitis; Restoring Nature's Homeostasis
• Official Title: Transplantation of Faeces in Ulcerative Colitis; Restoring Nature's Homeostasis.

Brief Summary

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.

• 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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Ulcerative Colitis

Intervention

• Other: treatment with faecal transplantation (donor faeces)
  faecal transplantation
• Other: treatment with faecal transplantation (own faeces)
  faecal transplantation

Study Arms

• 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.
  Intervention: Other: treatment with faecal transplantation (donor faeces)
• 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.
  Intervention: Other: treatment with faecal transplantation (own faeces)

• Publications *: Rossen NG, Fuentes S, van der Spek MJ, Tijssen JG, Hartman JH, Duflou A, Löwenberg 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 28, 2014): 50
• Original Estimated Enrollment (submitted: July 25, 2012): 40
• Actual Study Completion Date: December 2014
• Actual Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT01650038
• Other Study ID Numbers: METC 2011_005
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: C.Y. Ponsioen, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Study Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: Not Provided

Investigators

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

• PRS Account: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Verification Date: December 2014