Jan Březina1, Lukáš Bajer1, Pavel Wohl1, Dana Ďuricová2, Pavel Hrabák3, Aleš Novotný3, Jana Koželuhová4, Milan Lukáš2, Jakub Mrázek5, Kateřina Olša Fliegerová5, Simona Kvasnová5, Mekadim Chahrazed5, Jan Mareš1, Julius Špičák1, Pavel Drastich1. 1. Hepatogastroenterology Department, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic. 2. Clinical and Research Centre for IBD ISCARE, 19000 Prague, Czech Republic. 3. 4th Department of Medicine-Department of Gastroenterology and Hepatology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12808 Prague, Czech Republic. 4. Gastroenterology Department, I. Internal Clinic, University Hospital in Pilsen, 30100 Pilsen, Czech Republic. 5. Institute of Animal Physiology and Genetics of the Czech Academy of Science, v.v.i., 14220 Prague, Czech Republic.
Abstract
BACKGROUND AND AIMS: Ulcerative colitis (UC) is a chronic inflammatory disease. Fecal microbial transplantation (FMT) is a promising alternative treatment. METHODS: This multicenter, open-label, noninferiority trial randomized patients with active left-sided UC (Mayo score 4-10) equally to FMT or 5-aminosalicylic acid (5-ASA) enemas. FMT enemas were administered five times in the first week and then once weekly for 5 weeks. 5-ASA enemas were administered daily for 2 weeks and then every other day. The primary study endpoint was clinical remission, with a total Mayo score ≤2 at week 12 with no subscore >1. RESULTS:Sixty-one patients were screened; 45 were enrolled and randomized toFMT (n = 23) or 5-ASA (n = 22). Twenty-one FMT and 22 5-ASA patients completed at least the week 4 study visit and were included in the mITT analysis. Twelve FMT (57%) and eight 5-ASA patients achieved the primary study endpoint. FMT noninferiority with 10% margin was confirmed (95% CI: -7.6%, 48.9%). Adverse events occurred in 12 FMT (57%) and 13 5-ASA (59%) patients. Increased microbial diversity persisted 3 months after FMT. CONCLUSION:FMT is an effective treatment for left-sided UC and increased recipient microbiome diversity. Targeted microbiome modification may improve FMT efficacy. Further investigation is needed to guide donor and patient selection.
RCT Entities:
BACKGROUND AND AIMS: Ulcerative colitis (UC) is a chronic inflammatory disease. Fecal microbial transplantation (FMT) is a promising alternative treatment. METHODS: This multicenter, open-label, noninferiority trial randomized patients with active left-sided UC (Mayo score 4-10) equally to FMT or 5-aminosalicylic acid (5-ASA) enemas. FMT enemas were administered five times in the first week and then once weekly for 5 weeks. 5-ASA enemas were administered daily for 2 weeks and then every other day. The primary study endpoint was clinical remission, with a total Mayo score ≤2 at week 12 with no subscore >1. RESULTS: Sixty-one patients were screened; 45 were enrolled and randomized to FMT (n = 23) or 5-ASA (n = 22). Twenty-one FMT and 22 5-ASApatients completed at least the week 4 study visit and were included in the mITT analysis. Twelve FMT (57%) and eight 5-ASApatients achieved the primary study endpoint. FMT noninferiority with 10% margin was confirmed (95% CI: -7.6%, 48.9%). Adverse events occurred in 12 FMT (57%) and 13 5-ASA (59%) patients. Increased microbial diversity persisted 3 months after FMT. CONCLUSION:FMT is an effective treatment for left-sided UC and increased recipient microbiome diversity. Targeted microbiome modification may improve FMT efficacy. Further investigation is needed to guide donor and patient selection.
Authors: John Gubatan; Theresa Louise Boye; Michelle Temby; Raoul S Sojwal; Derek R Holman; Sidhartha R Sinha; Stephan R Rogalla; Ole Haagen Nielsen Journal: Microorganisms Date: 2022-07-07