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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Other: treatment with faecal transplantation (donor faeces)
* Other: treatment with faecal transplantation (own faeces)


Participation Criteria
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Eligibility Criteria
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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

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: faecal transplantation; donor faeces<br>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)<br>* faecal transplantation<br>|
| Placebo Comparator: faecal transplantation; placebo<br>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)<br>* faecal transplantation<br>|

What is the study measuring?
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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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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faecal transplantation, ulcerative colitis, inflammatory bowel disease