Rigorous Donor Selection for Fecal Microbiota Transplantation in Active Ulcerative Colitis: Key Lessons From a Randomized Controlled Trial Halted for Futility.

Autor:	Caenepeel C; Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium., Deleu S; Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium., Vazquez Castellanos JF; Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven, Belgium., Arnauts K; Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium., Braekeleire S; Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium., Machiels K; Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium., Baert F; AZ Delta Roeselare, Department of Gastroenterology and Hepatology, Roeselare, Belgium., Mana F; University Hospitals Brussels, Department of Gastroenterology and Hepatology, Brussels, Belgium., Pouillon L; Imelda Hospital Bonheiden, Department of Gastroenterology and Hepatology, Bonheiden, Belgium., Hindryckx P; Ghent University Hospital, Department of Gastroenterology, Ghent, Belgium., Lobaton T; Ghent University Hospital, Department of Gastroenterology, Ghent, Belgium; Department of Internal Medicine and Paediatrics, Ghent University, Gent, Belgium., Louis E; Liège University Hospital, CHU Liège, Department of Gastroenterology and Hepatology, Liège, Belgium., Franchimont D; Erasmus Hospital Brussels, Department of Gastroenterology and Hepatology, Brussels, Belgium., Verstockt B; Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium., Ferrante M; Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium., Sabino J; Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium., Vieira-Silva S; Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium; Institute of Medical Microbiology and Hygiene and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Institute of Molecular Biology (IMB), Mainz, Germany., Falony G; Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven, Belgium; Institute of Medical Microbiology and Hygiene and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Raes J; Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven, Belgium., Vermeire S; Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium. Electronic address: severine.vermeire@uzleuven.be.
Jazyk:	angličtina
Zdroj:	Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association [Clin Gastroenterol Hepatol] 2024 May 23. Date of Electronic Publication: 2024 May 23.
DOI:	10.1016/j.cgh.2024.05.017
Abstrakt:	Background & Aims: Rigorous donor preselection on microbiota level, strict anaerobic processing, and repeated fecal microbiota transplantation (FMT) administration were hypothesized to improve FMT induction of remission in ulcerative colitis (UC). Methods: The RESTORE-UC trial was a multi-centric, double-blind, sham-controlled, randomized trial. Patients with moderate to severe UC (defined by total Mayo 4-10) were randomly allocated to receive 4 anaerobic-prepared allogenic or autologous donor FMTs. Allogenic donor material was selected after a rigorous screening based on microbial cell count, enterotype, and the abundance of specific genera. The primary endpoint was steroid-free clinical remission (total Mayo ≤2, no sub-score >1) at week 8. A pre-planned futility analysis was performed after 66% (n = 72) of intended inclusions (n = 108). Quantitative microbiome profiling (n = 44) was performed at weeks 0 and 8. Results: In total, 72 patients were included, of which 66 received at least 1 FMT (allogenic FMT, n = 30 and autologous FMT, n = 36). At week 8, respectively, 3 and 5 patients reached the primary endpoint of steroid-free clinical remission (P = .72), indicating no treatment difference of at least 5% in favor of allogenic FMT. Hence, the study was stopped due to futility. Microbiome analysis showed numerically more enterotype transitions upon allogenic FMT compared with autologous FMT, and more transitions were observed when patients were treated with a different enterotype than their own at baseline (P = .01). Primary response was associated with lower total Mayo scores, lower bacterial cell counts, and higher Bacteroides 2 prevalence at baseline. Conclusion: The RESTORE-UC trial did not meet its primary endpoint of increased steroid-free clinical remission at week 8. Further research should additionally consider patient selection, sterilized sham-control, increased frequency, density, and viability of FMT prior to administration. Clinicaltrials: gov, Number: NCT03110289. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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