Safety and efficacy of faecal microbiota transplantation by Anaerobic Cultivated Human Intestinal Microbiome (ACHIM) in patients with systemic sclerosis: study protocol for the randomised controlled phase II ReSScue trial.

Autor:	Hoffmann-Vold AM; Department of Rheumatology, Oslo University Hospital, Oslo, Norway a.m.hoffmann-vold@medisin.uio.no.; Faculty of medicine, University of Oslo, Oslo, Norway., Fretheim HH; Department of Rheumatology, Oslo University Hospital, Oslo, Norway.; Faculty of medicine, University of Oslo, Oslo, Norway., Sarna VK; Department of gastroenterology, Oslo University Hospital, Oslo, Norway., Barua I; Department of Rheumatology, Oslo University Hospital, Oslo, Norway.; Faculty of medicine, University of Oslo, Oslo, Norway., Carstens MN; Department of Rheumatology, Oslo University Hospital, Oslo, Norway., Distler O; Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland., Khanna D; Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA., Volkmann ER; Division of Rheumatology, David Geffen School of Medicine, Los Angeles, California, USA., Midtvedt Ø; Department of Rheumatology, Oslo University Hospital, Oslo, Norway., Didriksen H; Department of Rheumatology, Oslo University Hospital, Oslo, Norway.; Faculty of medicine, University of Oslo, Oslo, Norway., Dhainaut A; Department of Rheumatology, St Olavs Hospital Universitetssykehuset i Trondheim, Trondheim, Norway., Halse AK; Department of Rheumatology, University of Bergen, Bergen, Hordaland, Norway., Bakland G; Department of Rheumatology, University Hospital of North Norway, Tromso, Troms, Norway., Pesonen M; Oslo Centre for Biostatistics & Epidemiology, Oslo University Hospital, Oslo, Norway., Olsen I; Oslo Centre for Biostatistics & Epidemiology, Oslo University Hospital, Oslo, Norway., Molberg Ø; Department of Rheumatology, Oslo University Hospital, Oslo, Norway.; Faculty of medicine, University of Oslo, Oslo, Norway.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2021 Jun 24; Vol. 11 (6), pp. e048541. Date of Electronic Publication: 2021 Jun 24.
DOI:	10.1136/bmjopen-2020-048541
Abstrakt:	Introduction: In the multisystem inflammatory disorder systemic sclerosis (SSc), gastrointestinal tract (GIT) affliction is highly prevalent. There are no known disease modifying therapies and the negative impact is substantial. Aiming for a new therapeutic principle, and inspired by recent work showing associations between gut microbiota changes and GIT symptoms in SSc, we performed a pilot study on faecal microbiota transplantation (FMT) with the single-donor bacterial culture 'Anaerobic Cultivated Human Intestinal Microbiome (ACHIM)'. Motivated by positive pilot study signals, we designed the ReSScue trial as a phase II multicentre, placebo-controlled, randomised 20-week trial to evaluate safety and efficacy on lower GIT symptoms of FMT by ACHIM in SSc. Methods and Analyses: We aim to include 70 SSc participants with moderate to severe lower GIT symptoms, defined by the validated patient-reported University of California Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 2.0 questionnaire. The trial includes three parts. In part A1 (induction phase) lasting from week 0 to week 12, participants will be randomised 1:1 to repeat infusions of 30 mL ACHIM or placebo at week 0 and 2 by gastroduodenoscopy. In part A2, which is an 8-week subsequent maintenance phase, all study participants will receive 30 mL ACHIM at week 12 and followed until week 20 on continued blind. In part B, which will last until the last participant completes part A2, the participants will be followed through a maximum 16-week extended monitoring period, for longer-term data on safety and intervention effects. Primary endpoint is change from baseline to week 12 in UCLA GIT subscale scores of diarrhoea or bloating, depending on the worst symptom at baseline evaluated separately for each patient. Secondary endpoints are safety measures and changes in UCLA GIT scores (total, diarrhoea and bloating). Ethics and Dissemination: This protocol was approved by the Northern Norwegian Committee for Medical Ethics. Study findings will be published. Trial Registration Number: NCT04300426; Pre-results. Protocol Version: V.3.1. Competing Interests: Competing interests: A-MH-V: Actelion, ARXX, Bayer, Boehringer Ingelheim, Medscape, Merck Sharp & Dohme, Lilly and Roche. OD: Abbvie, Acceleron Pharma, Amgen, AnaMar, Bayer, Boehringer Ingelheim, Catenion, Drug Development International, CSL Behring, ChemomAb, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, Italfarmaco, iQvia, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Target Bio Science and UCB in the area of potential treatments of scleroderma and its complications. In addition, OD has a patent mir-29 for the treatment of systemic sclerosis issued (US8247389, EP2331143). DK: Abbvie, Actelion/Janssen, Acceleron Pharma, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, GSK, Horizon Pharmaceuticals, Mitsubishi Tanabe Pharma, Pfizer, Roche, Sanofi, United Therapeutics. DK is chief medical officer of Eicos Sciences. ERV: Disclosures unrelated to the manuscript: Grants (Corbus, Forbius, Boehringer Ingelheim); Consulting fees (Boehringer Ingelheim). ØMi: Son of owner of ACHIM. (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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