Transfer of FRozen Encapsulated multi-donor Stool filtrate for active ulcerative Colitis (FRESCO): study protocol for a prospective, multicenter, double-blind, randomized, controlled trial
Andreas Stallmach,
Philip Grunert,
Johannes Stallhofer,
Bettina Löffler,
Michael Baier,
Jürgen Rödel,
Michael Kiehntopf,
Sophie Neugebauer,
Dietmar H. Pieper,
Howard Junca,
Andrea Tannapfel,
Ute Merkel,
Ulrike Schumacher,
Maria Breternitz-Gruhne,
Tabitha Heller,
Anja Schauer,
Michael Hartmann,
Arndt Steube
Affiliations
Andreas Stallmach
Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena
Philip Grunert
Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena
Johannes Stallhofer
Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena
Bettina Löffler
Institute of Medical Microbiology, Jena University Hospital, Friedrich Schiller University
Michael Baier
Institute of Medical Microbiology, Jena University Hospital, Friedrich Schiller University
Jürgen Rödel
Institute of Medical Microbiology, Jena University Hospital, Friedrich Schiller University
Michael Kiehntopf
Institute for Clinical Chemistry and Laboratory Diagnostics and Integrated Biobank Jena, Jena University Hospital
Sophie Neugebauer
Institute for Clinical Chemistry and Laboratory Diagnostics and Integrated Biobank Jena, Jena University Hospital
Dietmar H. Pieper
Microbial Interactions and Processes Research Group, Helmholtz Centre for Infection
Howard Junca
Microbial Interactions and Processes Research Group, Helmholtz Centre for Infection
Andrea Tannapfel
Institute for Pathology, Ruhr University
Ute Merkel
Hospital Pharmacy, Jena University Hospital
Ulrike Schumacher
Center for Clinical Studies Jena (ZKS), Jena University Hospital
Maria Breternitz-Gruhne
Center for Clinical Studies Jena (ZKS), Jena University Hospital
Tabitha Heller
Center for Clinical Studies Jena (ZKS), Jena University Hospital
Anja Schauer
Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena
Michael Hartmann
Hospital Pharmacy, Jena University Hospital
Arndt Steube
Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena
Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease with significant morbidity and mortality. Although the precise cause remains unknown, disturbances in the intestinal microbial community have been linked to its pathogenesis. Randomized controlled trials in UC and relapsing Clostridioides difficile infection (CDI) have established fecal microbiota (FM) transfer (FMT) as an effective therapy. In this context, preliminary results indicated that the transfer of sterile fecal microbiota filtrates (<0.2 μm; FMF, FMFT) of donor stool also drives gastrointestinal microbiota changes and eliminates symptoms in CDI patients. However, along with the success of FMT, regulatory agencies issued safety alerts following reports of serious adverse events due to transmission of enteric pathogens through FMT. To reduce this risk, we established an extensive test protocol for our donors and quarantine regulations for the produced capsules, but alternative concepts are desirable. Methods Our project is a randomized, controlled, longitudinal, prospective, three-arm, multicenter, double-blind study to determine the safety and efficacy of repeated long-term, multi-donor FM or FMF transfers compared to placebo using oral, frozen capsules in 174 randomized patients with mild to moderate active UC. The primary outcome will be clinical remission at week 12. Discussion This proposal aims to examine (a) the efficacy of encapsulated transfer of FM and FMF as a therapy for mild to moderate UC, (b) the short- and long-term safety of FMT and FMFT in patients with UC, and (c) the microbial and immunologic changes that occur after FMT and FMFT to help understand how and why it affects inflammatory bowel disease. Trial registration ClinicalTrials.gov NCT03843385 . DRKS (Deutsches Register für Klinische Studien) DRKS00020471
