Transfer of Feces in Ulcerative Colitis 2

Study Overview
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Brief Summary
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The goal of this placebo-controlled randomised multicenter trial is to evaluate the efficacy and safety of anaerobic prepared donor fecal microbiota transplantation (FMT) compared to autologous FMT in patient with ulcerative colitis. Participants will receive 4 treatments with frozen FMT via both upper and lower gastro-intestinal route (infusion via duodenal tube and enemas). Donors are selected based on microbiota profile.

Official Title
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Transfer of Feces in Ulcerative Colitis 2; Improving Efficacy

Conditions
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Ulcerative Colitis, Ulcerative Colitis Flare, Ulcerative Colitis Acute

Intervention / Treatment
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* Other: Fecal microbiota transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 and <70 Ability to give informed consent Established ulcerative colitis with known involvement of the left colon according to the Lennard-Jones criteria Partial mayo score of ≥ 3 and calprotectin > 250 Full Mayo score 5-9 Endoscopic Mayo score of ≥2 in either the rectum or sigmoid upon screening sigmoidoscopy Stable dose of thiopurines or , 5-ASA, or budesonide in preceding 8 weeks. Stable dose of budesonide in preceding 2 weeks. Prednisone use ≤15mg/day in preceding 2 weeks with a mandatory taper of 5 mg per week starting from week 4. Women need to use reliable contraceptives during participation in the study Alkaline phosphatase > 1.5 x ULN in the subgroup of PSC/UC patients. Exclusion Criteria: Condition leading to profound immunosuppression For example: HIV, infectious diseases leading to immunosuppression, bone marrow malignancies Use of systemic chemotherapy Child-Pugh B liver cirrhosis Anti-TNFα treatment in preceding 2 months Vedolizumab treatment in preceding 2 months Tofacitinib treatment in preceding 2 months Ustekinumab treatment in preceding 2 months Cyclosporine treatment in preceding 4 weeks Use of Methotrexate in preceding 2 months Prednisolone dose > 15 mg/day in preceding 2 weeks Use of topical therapy in preceding 2 weeks Life expectancy < 12 months Difficulty with swallowing Use of systemic antibiotics in preceding 4 weeks Use of probiotic treatment in preceding 4 weeks Positive stool cultures for common enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, enteropathogenic e coli) Positive C. Difficile stool test Positive dual faeces test for pathogenic parasites e.g. Dientamoeba histolytica, Giardia Lamblia, Dientamoeba fragilis, Blastocystis hominis only if microscopically many or very many blastocysts are seen. Positive serological test for HIV History of surgery: presence of a pouch presence of stoma Known intra-abdominal fistula Pregnancy or women who give breastfeeding Vasopressive medication, icu stay Signs of ileus, diminished passage Allergy to macrogol or substituents, eg peanuts, shellfish Known allergy to iv gadolinium in the subgroup of patients who would be scheduled for MRI liver Crohn's disease Subject who has any conditions that in the opinion of the investigator, would compromise the safety of the subject or the quality of the data and is an unsuitable candidate for the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donor fecal microbiota transplant<br> | Other: Fecal microbiota transplant<br>* Frozen FMT via duodenal tube (2 times) and enemas (4 times)<br>* Other names: FMT;|
| Placebo Comparator: Autologous fecal microbiota transplant<br> | Other: Fecal microbiota transplant<br>* Frozen FMT via duodenal tube (2 times) and enemas (4 times)<br>* Other names: FMT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical and endoscopic remission | per adapted Mayo: stool frequency subscores (SFS) ≤ 1, rectal bleeding subscore (RBS) =0 and endoscopic subscore ≤ 1. The adapted Mayo score has a minimum score of 0 and a maximum score of 9. The 3 subscores (SFS, RBS, and endoscopic subscore) have a minimum of 0 and a maximum score of 3. The adapted Mayo score does not include PGA (physician global assessment), in contrary to the full Mayo score. A higher score reflects worse outcome. | week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response | Adapted Mayo: decrease from baseline ≥ 2 points and ≥ 30% plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1. The adapted Mayo score has a minimum score of 0 and a maximum score of 9. The 3 subscores (SFS, RBS, and endoscopic subscore) have a minimum of 0 and a maximum score of 3. The adapted Mayo score does not include PGA (physician global assessment), in contrary to the full Mayo score. | week 8 | 
| Endoscopic response, evaluated by sigmoidoscopy | •Proportion of patients with ≥1 point reduction in summed endoscopic Mayo score of both the rectum and sigmoid. | week 8 |