1 Hoffmann-Vold A-M, et al. BMJ Open 2021;11:e048541. doi:10.1136/bmjopen-2020-048541 Open access Safety and effcacy 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 Anna-Maria Hoffmann-Vold , 1,2 Håvard H Fretheim, 1,2 Vikas K Sarna, 3 Imon Barua, 1,2 Maylen N Carstens, 1 Oliver Distler, 4 Dinesh Khanna , 5 Elizabeth R Volkmann, 6 Øyvind Midtvedt, 1 Henriette Didriksen, 1,2 Alvilde Dhainaut, 7 Anne-Kristine Halse, 8 Gunnstein Bakland, 9 Maiju Pesonen, 10 Inge Olsen, 10 Øyvind Molberg 1,2 To cite: Hoffmann-Vold A-M, Fretheim HH, Sarna VK, et al. Safety and effcacy 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. BMJ Open 2021;11:e048541. doi:10.1136/ bmjopen-2020-048541 ► Prepublication history and additional online supplemental material for this paper are available online. To view these fles, please visit the journal online (http://dx.doi.org/10. 1136/bmjopen-2020-048541). Received 30 December 2020 Accepted 01 June 2021 For numbered affliations see end of article. Correspondence to Dr Anna-Maria Hoffmann-Vold; a.m.hoffmann-vold@medisin. uio.no Protocol © 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. ABSTRACT 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 fndings will be published. Trial registration number NCT04300426; Pre-results. Protocol version V.3.1. INTRODUCTION Systemic sclerosis (SSc) is a rare, multiorgan system disorder with a marked negative impact on quality of life and reduced survival, with gastrointestinal tract (GIT) involvement as a major contributor to both. 1–5 There are no specific therapies available for SSc-related GIT disease, but symptomatic relief can be provided by some agents, including proton pump inhibitors. 3 6 7 Understanding of mech- anisms behind SSc-related GIT disease is poor. However, it is known that alterations of the gut microbiota (dysbiosis) exist in SSc and associate with specific GIT symptoms. However, the question of how these alter- ations affect the pathogenesis of this disease and correlate with SSc symptoms still remains. In terms of GIT symptoms, there is evidence Strengths and limitations of this study ► This study is a randomised clinical trial. ► The feasibility of reproduction is high due to the use of Anaerobic Cultivated Human Intestinal Microbiome. ► Long-term safety data will be available. ► The effcacy cannot be assessed beyond the 12- week study period. Protected by copyright. on September 28, 2021 at Universitetsbiblioteket i Tromsoe. http://bmjopen.bmj.com/ BMJ Open: first published as 10.1136/bmjopen-2020-048541 on 24 June 2021. Downloaded from