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

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)50 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

Time frame: at 12 weeks after treatment.

Secondary Outcomes

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