FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial
Introduction Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). The strong association between gut and liver inflammation has driven several pathogenic hypotheses to which the intestinal microbiome is proposed to contribute. Pilot s...
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BMJ Publishing Group
2025-01-01
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| author | Laith Alrubaiy Rachel Cooney Tariq Iqbal Mohammed Nabil Quraishi Susan Manzoor Christopher Quince Palak J Trivedi Andrew D Beggs Alexandra Vince Chris Weston Benjamin Mullish Sahida Shabir Nicola Jackson Anna Rowe Victoria Homer Willem van Schaik Peter Rimmer Sarah Al-Shakhshir Arzoo Patel Derick Gyimah Miriam Hares Elena Efstathiou |
| author_facet | Laith Alrubaiy Rachel Cooney Tariq Iqbal Mohammed Nabil Quraishi Susan Manzoor Christopher Quince Palak J Trivedi Andrew D Beggs Alexandra Vince Chris Weston Benjamin Mullish Sahida Shabir Nicola Jackson Anna Rowe Victoria Homer Willem van Schaik Peter Rimmer Sarah Al-Shakhshir Arzoo Patel Derick Gyimah Miriam Hares Elena Efstathiou |
| author_sort | Laith Alrubaiy |
| collection | DOAJ |
| description | Introduction Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). The strong association between gut and liver inflammation has driven several pathogenic hypotheses to which the intestinal microbiome is proposed to contribute. Pilot studies of faecal microbiota transplantation (FMT) in PSC and IBD are demonstrated to be safe and associated with increased gut bacterial diversity. However, the longevity of such changes and the impact on markers of disease activity and disease progression have not been studied. The aim of this clinical trial is to determine the effects of repeated FMT as a treatment for PSC-IBD.Methods and analysis FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO) is a phase IIa randomised placebo-controlled trial to assess the efficacy and safety of repeated colonic administration of FMT in patients with non-cirrhotic PSC-IBD. Fifty-eight patients will be recruited from six sites across England and randomised in a 1:1 ratio between active FMT or FMT placebo arms. FMT will be manufactured by the University of Birmingham Microbiome Treatment Centre, using stool collected from rigorously screened healthy donors. A total of 8 weekly treatments will be delivered; the first through colonoscopic administration (week 1) and the remaining seven via once-weekly enema (up to week 8). Participants will then be followed on a 12-weekly basis until week 48 from the first treatment visit. The primary efficacy outcome will be to determine the effect of FMT on serum alkaline phosphatase values over time (end of study at 48 weeks). Key secondary outcomes will be to evaluate the impact of FMT on other liver biochemical parameters, PSC risk scores, circulating and imaging markers of liver fibrosis, health-related quality of life measures, IBD activity and the incidence of PSC-related clinical events. Key translational objectives will be to identify mucosal metagenomic, metatranscriptomic, metabolomic and immunological pathways associated with the administration of FMT.Ethics and dissemination The protocol was approved by the South Central—Hampshire B Research Ethics Committee (REC 23/SC/0147). Participants will be required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.Trial registration number The trial was registered at ClinicalTrials.gov on 23 February 2024 (NCT06286709). Weblink: Study Details | FAecal Microbiota Transplantation in primaRy sclerosinG chOlangitis | ClinicalTrials.gov. |
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| institution | Kabale University |
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| publishDate | 2025-01-01 |
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| spelling | doaj-art-4a364bb4b5cd46879d26c2e8c3aa6d7e2025-01-07T06:45:09ZengBMJ Publishing GroupBMJ Open2044-60552025-01-0115110.1136/bmjopen-2024-095392FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trialLaith Alrubaiy0Rachel Cooney1Tariq Iqbal2Mohammed Nabil Quraishi3Susan Manzoor4Christopher Quince5Palak J Trivedi6Andrew D Beggs7Alexandra Vince8Chris Weston9Benjamin Mullish10Sahida Shabir11Nicola Jackson12Anna Rowe13Victoria Homer14Willem van Schaik15Peter Rimmer16Sarah Al-Shakhshir17Arzoo Patel18Derick Gyimah19Miriam Hares20Elena Efstathiou218 Gastroenterology, St Mark`s Hospital and Academic Institute, London, UK2 University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK2 University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK3 University of Birmingham Institute of Cancer and Genomic Sciences, Birmingham, Birmingham, UK7 University of Birmingham Microbiome Treatment Centre, University of Birmingham, Birmingham, UK9 Food, Microbiome and Health Institute Strategic Programme, Quadram Institute Bioscience, Norwich, UK1 National Institute of Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC) Center for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, England, UK2 University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK6 Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK1 National Institute of Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC) Center for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, England, UK4 Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London Faculty of Medicine, London, UK7 University of Birmingham Microbiome Treatment Centre, University of Birmingham, Birmingham, UK6 Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK6 Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK6 Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK11 Institute of Microbiology and Infection, University of Birmingham, Birmingham, England, UK2 University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK1 National Institute of Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC) Center for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, England, UK1 National Institute of Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC) Center for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, England, UK6 Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK11 Institute of Microbiology and Infection, University of Birmingham, Birmingham, England, UK3 University of Birmingham Institute of Cancer and Genomic Sciences, Birmingham, Birmingham, UKIntroduction Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). The strong association between gut and liver inflammation has driven several pathogenic hypotheses to which the intestinal microbiome is proposed to contribute. Pilot studies of faecal microbiota transplantation (FMT) in PSC and IBD are demonstrated to be safe and associated with increased gut bacterial diversity. However, the longevity of such changes and the impact on markers of disease activity and disease progression have not been studied. The aim of this clinical trial is to determine the effects of repeated FMT as a treatment for PSC-IBD.Methods and analysis FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO) is a phase IIa randomised placebo-controlled trial to assess the efficacy and safety of repeated colonic administration of FMT in patients with non-cirrhotic PSC-IBD. Fifty-eight patients will be recruited from six sites across England and randomised in a 1:1 ratio between active FMT or FMT placebo arms. FMT will be manufactured by the University of Birmingham Microbiome Treatment Centre, using stool collected from rigorously screened healthy donors. A total of 8 weekly treatments will be delivered; the first through colonoscopic administration (week 1) and the remaining seven via once-weekly enema (up to week 8). Participants will then be followed on a 12-weekly basis until week 48 from the first treatment visit. The primary efficacy outcome will be to determine the effect of FMT on serum alkaline phosphatase values over time (end of study at 48 weeks). Key secondary outcomes will be to evaluate the impact of FMT on other liver biochemical parameters, PSC risk scores, circulating and imaging markers of liver fibrosis, health-related quality of life measures, IBD activity and the incidence of PSC-related clinical events. Key translational objectives will be to identify mucosal metagenomic, metatranscriptomic, metabolomic and immunological pathways associated with the administration of FMT.Ethics and dissemination The protocol was approved by the South Central—Hampshire B Research Ethics Committee (REC 23/SC/0147). Participants will be required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.Trial registration number The trial was registered at ClinicalTrials.gov on 23 February 2024 (NCT06286709). Weblink: Study Details | FAecal Microbiota Transplantation in primaRy sclerosinG chOlangitis | ClinicalTrials.gov.https://bmjopen.bmj.com/content/15/1/e095392.full |
| spellingShingle | Laith Alrubaiy Rachel Cooney Tariq Iqbal Mohammed Nabil Quraishi Susan Manzoor Christopher Quince Palak J Trivedi Andrew D Beggs Alexandra Vince Chris Weston Benjamin Mullish Sahida Shabir Nicola Jackson Anna Rowe Victoria Homer Willem van Schaik Peter Rimmer Sarah Al-Shakhshir Arzoo Patel Derick Gyimah Miriam Hares Elena Efstathiou FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial BMJ Open |
| title | FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial |
| title_full | FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial |
| title_fullStr | FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial |
| title_full_unstemmed | FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial |
| title_short | FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial |
| title_sort | faecal microbiota transplantation in primary sclerosing cholangitis fargo study protocol for a randomised multicentre phase iia placebo controlled trial |
| url | https://bmjopen.bmj.com/content/15/1/e095392.full |
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