Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. UC pathogenesis remains poorly understood but involves an inappropriate immune response toward an unbalanced gut microbiota (called dysbiosis) in predisposed hosts. The purpose of this study is to determine the effect of the fecal microbiota transplantation on UC.
Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease affecting approximately 90 000 patients in France, mostly at young age, and altering their quality of life. Conventional Immunosuppressive treatment (ie azathioprine, anti-TNF (tumor necrosis factor ), vedolizumab) used in UC are expensive and associated with potentially severe complications such as infections and cancers. UC pathogenesis remains poorly understood but involves an inappropriate immune response toward an unbalanced gut microbiota (called dysbiosis) in predisposed hosts. Fecal microbiota transplantation (FMT) is now recommended in guidelines for treating recurrent Clostridium difficile infection. Although the pathogenesis involved in UC is different, FMT is a potential therapeutic strategy as transferring a healthy microbiota in an UC patient could restore the appropriate host-microbiota crosstalk. As the gut microbiota is dramatically altered by intestinal inflammation, transferring a massive amount of microbial organisms in an inflamed gut with epithelial barrier disruption might be a suboptimal strategy and could even have detrimental effects by allowing bacterial translocation. Thus, it's possible that performing FMT in UC patients who achieved remission after conventional treatment might be associated with better clinical outcome than in patients with active disease.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
150
The colonoscopy for FMT will be planned as soon as possible and never more than 5 weeks after inclusion visit. After colon cleansing using Polyethylen glycol, the patient will have a colonoscopy under general anesthesia. The patient will then receive either FMT (frozen preparation of 50g of stools in 300ml of physio, see donor section for details) or sham transplantation (FMT vehicle) in the cecum.
The sham-transplantation will be planned as soon as possible and never more than 5 weeks after inclusion visit. After colon cleansing using Polyethylen glycol, the patient will have a colonoscopy under general anesthesia. The patient will then sham transplantation (FMT vehicle) in the cecum.
Service de Gastroentérologie et Nutrition Hôpital Saint Antoine
Paris, Paris, France
Steroid-free clinical and endoscopic remission
Steroid-free clinical and endoscopic remission defined as a total Mayo score of 2 or lower and no subscore higher than 1 and mucosal healing defined as an endoscopic subscore of 0 or 1 (Sigmoidoscopy).
Time frame: 12 weeks after FMT or sham-transplantation
Steroid-free clinical remission
Steroid-free clinical remission defined as a Partial Mayo Clinic score of 0 or 1
Time frame: 12 weeks after FMT or sham-transplantation
Steroid-free clinical remission
Steroid-free clinical remission defined as a Partial Mayo Clinic score of 0 or 1
Time frame: 24 weeks after FMT or sham-transplantation
Steroid-free endoscopic response
Steroid-free endoscopic response defined as a Mayo endoscopy subscore of 1 or less, with a reduction of at least 1 point from baseline
Time frame: 12 weeks after FMTor sham-transplantation
Steroid-free endoscopic remission
Steroid-free endoscopic remission defined as an Endoscopic Mayo Clinic score of 0
Time frame: 12 weeks after FMT or sham-transplantation
Microbiota composition and diversity
Microbiota composition and diversity assessed by 16s sequencing compared to baseline and to donor's microbiota.
Time frame: 12 and 24 weeks after FMT or sham-transplantation
Proportion of adverse events in each group
abdominal pain, nausea, vomiting, fever, modified intestinal transit and episode of infection
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Time frame: Through study completion, up to 25 months and one week
Inflammatory biological parameter 1
CRP
Time frame: up to 24 weeks
Inflammatory biological parameter 2
fecal calprotectin
Time frame: up to 24 weeks
Inflammatory biological parameter 3
platelet number
Time frame: up to 24 weeks
Endoscopic lesions
Endoscopic lesions at coloscopy and sigmoidoscopy by endoscopic Mayo score
Time frame: 12 weeks after FMT or sham-transplantation
Endoscopic lesions
Endoscopic lesions at coloscopy (baseline) and sigmoidoscopy by UCEIS score
Time frame: 12 weeks after FMT or sham-transplantation