{
  "abstract": "Introduction The interaction between the gut microbiota and the host immune system is implicated in the pathogenesis of inflammatory bowel disease, including ulcerative colitis (UC). Targeting the gut microbiota with faecal microbiota transplantation (FMT) from a healthy donor has shown promise in inducing remission in patients with active UC. However, mixed results and protocol heterogeneity have limited its practical application. Our previous Transfer of Faeces in Ulcerative Colitis; Restoring Homeostasis (TURN) trial found a correlation of clinical response with specific strains and butyrate production. Since most gut microbes, including many butyrate producers, are anaerobes, anoxic processing of donor stool may be essential to increase efficacy of FMT in UC. This trial aims to enhance FMT efficacy by applying strict anoxic processing, selecting donors based on microbial composition and using repetitive dual-route administration.Methods and analysis This randomised, double-blind, placebo-controlled, multicentre study evaluates the efficacy of strictly anoxic prepared donor FMT compared with anoxic prepared autologous FMT in patients with mild to moderate active UC. An open-label extension option is available for non-responders in the autologous arm. Included patients will receive 4 weekly FMTs, comprising two double-route administrations (nasoduodenal administration combined with enema) and two single enemas. Donors are selected based on their microbiota profile, informed by our previous TURN trial and literature. A total of 76 patients evaluable for the primary endpoint will be included. The primary endpoint is steroid-free clinical and endoscopic remission at week 8, assessed by the adapted Mayo score. An interim analysis will be conducted midway through the study by a Data Safety Monitoring Board to monitor efficacy and safety. Other outcomes of this study include the evaluation of clinical, endoscopic and histological response. In addition to clinical results, this study aims to provide valuable insights into specific microbial strains, metabolites and mechanisms correlated with response, aiding in the development of future microbial therapies.Ethics and dissemination Ethics approval was obtained from the medical ethics committee of the Amsterdam University Medical Centre in the Netherlands (reference number 2018_057). All participants will provide written informed consent. The results of the trial will be disseminated through publication in a peer-reviewed journal and presentations at (inter)national conferences.Trial registration number Prospectively registered in May 2018 in the Dutch Trial Register (NTR/LTR) as NL7770. Assigned NL-OMON52507 following the transition of the Dutch Trial Register to the Overview of Medical Research in the Netherlands. Also registered at ClinicalTrials.gov ( NCT05998213).",
  "authors": [
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands"
      ],
      "name": "Mèlanie V Bénard"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands"
      ],
      "name": "Mirjam JW Van Der Spek"
    },
    {
      "affiliations": [
        "Microbiota Center Amsterdam (MiCA), Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands",
        "Department of Experimental Vascular Medicine, Amsterdam UMC Location AMC, Amsterdam, The Netherlands"
      ],
      "name": "Mark Davids"
    },
    {
      "affiliations": [
        "Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, Amsterdam, The Netherlands"
      ],
      "name": "Caroline E Visser"
    },
    {
      "affiliations": [
        "Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands"
      ],
      "name": "Erwin G Zoetendal"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands"
      ],
      "name": "Bente Rethans"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands",
        "Amsterdam Gastroenterology Endocrinology and Metabolism, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands"
      ],
      "name": "Florine H Zwezerijnen-Jiwa"
    },
    {
      "affiliations": [
        "Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, The Netherlands"
      ],
      "name": "Marijn C Visschedijk"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands"
      ],
      "name": "Bas Oldenburg"
    },
    {
      "affiliations": [
        "Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, The Netherlands"
      ],
      "name": "Rinse K Weersma"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands"
      ],
      "name": "Cyriel Y Ponsioen"
    }
  ],
  "title": "Transfer of faeces in ulcerative colitis 2: improving efficacy – study protocol for a multicentre randomised controlled trial (TURN2 study)",
  "uid": "378dd57b-e8d8-5ea4-8421-97424100f750"
}