Effectiveness of Fecal Microbiota Transplantation as add-on Therapy in Mild-to-moderate Ulcerative Colitis

Study Overview
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Brief Summary
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Ulcerative colitis (UC) is a chronic immune-mediated inflammatory bowel disease (IBD) that almost always affects the rectum and often extends to the more proximal colon. UC usually begins at a young age (15-30 years), most patients (  85%) have a mild or moderate activity, characterized by periods of exacerbation and remission. Considering the important pathogenetic role of gut dysbiosis, recently, as an additional method of treating UC, it is considered a modification of altered gut microbiota using various drug and non-drug methods. One such method is fecal microbiota transplantation (FMT), consisting of the simultaneous replacement of the gut microbiota of a sick recipient with fecal material from a healthy donor. Even though so far the only officially approved indication for FMT is recurrent Clostridium difficile infection, however, the effectiveness of FMT is currently being studied in the treatment of other gastrointestinal and non-gastrointestinal pathologies, including UC. To date, several controlled and uncontrolled studies have been conducted to study the effectiveness of FMT in UC, showing encouraging results. This study aimed to assess the clinical and microbiological efficacy, tolerability, and safety of FMT as add-on therapy to basic therapy, in patients with mild-to-moderate UC.

Official Title
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Efficacy and Safety of Fecal Microbiota Transplantation as add-on Therapy in Patients With Mild-To-Moderate Ulcerative Colitis: A Randomized, Clinical Trial

Conditions
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Ulcerative Colitis Chronic Mild, Inflammatory Bowel Diseases

Intervention / Treatment
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* Drug: Mesalazine
* Biological: Fecal transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-60; Endoscopically and morphologically confirmed UC; Negative results of stool culture for the presence of pathogenic bacteria (Shigella spp., Salmonella spp., Campylobacter spp., Yersinia spp.) and toxin-producing Clostridioides difficile; partial Mayo score of 4-6; Mayo endoscopic subscore ≥1; Fecal calprotectin > 150 mcg/g Treatment with mesalazine at a daily dose of 3 g during the last 4 weeks Exclusion Criteria: Pregnancy, planning pregnancy or breastfeeding; Postponed operations on the abdominal cavity; Severe mental disorders, alcohol or drug abuse; Use of systemic corticosteroids, biological agents, and probiotics within 8 weeks before study Any condition or circumstance that would, in the opinion of the investigator, prevent completion of the study or interfere with analysis of study results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: standard care group<br>mesalazine (Pentasa) at a daily dose of 3 g (2 g orally + 1 g rectally) | Drug: Mesalazine<br>* daily dose of 3 g (2 g orally + 1 g rectally)<br>* Other names: Pentasa;|
| Experimental: Fecal transplantation<br>Fecal transplantation of fresh prepared feces from healthy donor. Application by colonoscope in proximal half of colon. | Biological: Fecal transplantation<br>* Preparation of fresh feces by blending in 0.9 % saline and crude filtering. The solution is applied in proximal colon of UC patient by colonoscopy after standard bowel preparation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in partial Mayo score > 2 points | Partial Mayo score composed of four parts: rectal bleeding, stool frequency, physician assessment, and endoscopy appearance. Each part is rated from 0 to 3, giving a total score of 0 to 12. Partial Mayo score (eliminates endoscopy) and of 2 to 4 points indicates mildly active disease, a score of 5 to 6 points indicates moderately active disease, and a score of 7 to 9 points indicates severely active disease | 8 weeks | 
| Changes in fecal calprotectin | expressed in µg/g | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiome profile change | Characterization of fecal microbiome by metagenomic analysis before and after intervention Characterization of fecal microbiome by metagenomic analysis before and after intervention | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative Colitis, fecal microbiota transplantation, gut microbiota, dysbiosis, inflammatory bowel disease