{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T21:31:15Z","timestamp":1794346275817,"version":"4.9.0"},"reference-count":21,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"unspecified","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Children\u2019s PSC Foundation"},{"name":"Associazione Malattie Autoimmuni del Fegato AMAF"},{"name":"Genetic s.p.a.","award":["The drug and the placebo pills are provided for fr"],"award-info":[{"award-number":["The drug and the placebo pills are provided for fr"]}]},{"name":"EpaC"},{"name":"Division of Gastroenterology, University of Milano-Bicocca","award":["The funder didn\u2019t influence the results\/outcomes"],"award-info":[{"award-number":["The funder didn\u2019t influence the results\/outcomes"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,12,15]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"\n Background<\/jats:title>\n Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). No therapy currently halts disease progression. The strong gut\u2013liver axis implicated in PSC pathogenesis supports the investigation of microbiome-targeted treatments. Oral vancomycin (OV), an antibiotic with potential immunomodulatory properties, has shown encouraging results in improving clinical symptoms and liver biochemistry in PSC. However, prospective data on its safety and efficacy remain limited.<\/jats:p>\n <\/jats:sec>\n \n Methods and analysis<\/jats:title>\n Oral Vancomycin for primary sclerosing Cholangitis in ITaly (VanC-IT) is a phase II, dose-finding, randomised, placebo-controlled, trial designed to evaluate the efficacy and safety of OV in patients with PSC, with or without underlying IBD. Adults and adolescents aged 15\u201375 years will be enrolled following a 10-week screening and run-in period and randomised in a 1:1:1 ratio to receive either placebo, OV 750\u2009mg\/day or OV 1500\u2009mg\/day for 24\u2009weeks. Randomisation will be stratified by baseline liver stiffness (< or \u226514.4\u2009kPa). Participants will be followed at 4 and 12 weeks post-treatment. The primary efficacy outcome is the change in serum alkaline phosphatase at 24\u2009weeks. Key secondary outcomes will assess the safety, the impact of OV on liver biochemistry, PSC risk scores, circulating and imaging markers of liver disease, IBD activity, quality of life and incidence of PSC-related clinical events. Key translational aims include sequencing of the faecal microbiota, metabolomic profiling of serum and stool samples and immunological profiling of serum associated with OV treatment.<\/jats:p>\n <\/jats:sec>\n \n Ethics and dissemination<\/jats:title>\n \n The protocol has been approved by the Ethics Committee CE Brianza on 10 February 2023, number 4017. Trial registration number\n NCT05876182<\/jats:ext-link>\n . 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.\n <\/jats:p>\n <\/jats:sec>\n \n Trial registration number<\/jats:title>\n \n NCT05876182<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-106630","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T14:40:30Z","timestamp":1767969630000},"page":"e106630","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Prospective, randomised, placebo-controlled, phase 2 clinical trial assessing the efficacy and safety of oral vancomycin in patients with primary sclerosing cholangitis with\/out inflammatory bowel disease in Italy: study protocol of VanC-IT trial"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct05876182","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05876182","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05876182","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Laura","family":"Cristoferi","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9028-4040","authenticated-orcid":false,"given":"Daphne","family":"D\u2019Amato","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare","family":"Maino","sequence":"additional","affiliation":[{"name":"Department of Radiology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8771-5428","authenticated-orcid":false,"given":"Davide","family":"Bernasconi","sequence":"additional","affiliation":[{"name":"Bicocca Bioinformatics Biostatistics and Bioimaging Centre-B4, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Emilio","family":"Dinelli","sequence":"additional","affiliation":[{"name":"Interventional Endoscopy Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio Maria Ivano","family":"Malandrin","sequence":"additional","affiliation":[{"name":"Microbiology Unit, Foundation IRCCS San Gerardo dei Tintori, Monza, MB, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Facciotti","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Vigan\u00f2","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Pirola","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Mario","family":"Festa","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5086-0514","authenticated-orcid":false,"given":"Alessio","family":"Gerussi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, Monza, Italy"},{"name":"Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Rossi","sequence":"additional","affiliation":[{"name":"Center of Biostatistics for Clinical Epidemiology, Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Malinverno","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Tettamanti","sequence":"additional","affiliation":[{"name":"Phase 1 Research Centre, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Elena","family":"Cazzaniga","sequence":"additional","affiliation":[{"name":"Phase 1 Research Centre, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Corso","sequence":"additional","affiliation":[{"name":"Department of Radiology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Ippolito","sequence":"additional","affiliation":[{"name":"Department of Radiology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Galimberti","sequence":"additional","affiliation":[{"name":"Bicocca Bioinformatics Biostatistics and Bioimaging Centre-B4, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Invernizzi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, Monza, Italy"},{"name":"Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Carbone","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy, Monza, Italy"},{"name":"Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"2026062609051570000_16.1.e106630.1","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1016\/S0140-6736(13)60096-3","article-title":"Primary sclerosing cholangitis","volume":"382","author":"Hirschfield","year":"2013","journal-title":"The Lancet"},{"key":"2026062609051570000_16.1.e106630.2","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1080\/00365521.2017.1421705","article-title":"Risk factors and prognosis for recurrent primary sclerosing cholangitis after liver transplantation: a Nordic Multicentre Study","volume":"53","author":"Lindstr\u00f6m","year":"2018","journal-title":"Scand J Gastroenterol"},{"key":"2026062609051570000_16.1.e106630.3","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17186591"},{"key":"2026062609051570000_16.1.e106630.4","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1053\/j.gastro.2020.05.049","article-title":"Effects of Primary Sclerosing Cholangitis on Risks of Cancer and Death in People With Inflammatory Bowel Disease, Based on Sex, Race, and Age","volume":"159","author":"Trivedi","year":"2020","journal-title":"Gastroenterology"},{"key":"2026062609051570000_16.1.e106630.5","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/s41586-022-04949-x","article-title":"Within-host evolution of a gut pathobiont facilitates liver translocation","volume":"607","author":"Yang","year":"2022","journal-title":"Nature New Biol"},{"key":"2026062609051570000_16.1.e106630.6","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1038\/s42255-021-00452-1","article-title":"Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signalling","volume":"3","author":"Schneider","year":"2021","journal-title":"Nat Metab"},{"key":"2026062609051570000_16.1.e106630.7","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.12.058"},{"key":"2026062609051570000_16.1.e106630.8","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.4254\/wjh.v13.i12.2113","article-title":"Use of oral vancomycin in children with autoimmune liver disease: A single centre expfile:\/\/\/Users\/Daphne\/Downloads\/ac9-8-e00577.pdferience","volume":"13","author":"Di","year":"2021","journal-title":"World J Hepatol"},{"key":"2026062609051570000_16.1.e106630.9","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1093\/gastro\/goab004","article-title":"Oral vancomycin in the treatment of primary sclerosing cholangitis-associated pouchitis","volume":"9","author":"Shen","year":"2021","journal-title":"Gastroenterol Rep (Oxf)"},{"key":"2026062609051570000_16.1.e106630.10","doi-asserted-by":"crossref","DOI":"10.14309\/crj.0000000000000577","article-title":"Microbiome Responses to Vancomycin Treatment in a Child With Primary Sclerosing Cholangitis and Ulcerative Colitis","volume":"8","author":"Britto","year":"2021","journal-title":"ACG Case Rep J"},{"key":"2026062609051570000_16.1.e106630.11","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1002\/hep.31702","article-title":"Oral Vancomycin or Ursodeoxycholic Acid for Pediatric Primary Sclerosing Cholangitis? The Uncontroversial Need for Randomized Controlled Trials","volume":"73","author":"Assis","year":"2021","journal-title":"Hepatology"},{"key":"2026062609051570000_16.1.e106630.12","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1007\/s12328-020-01296-0","article-title":"Successful response of primary sclerosing cholangitis and associated ulcerative colitis to oral vancomycin may depend on brand and personalized dose: report in an adolescent","volume":"14","author":"Buness","year":"2021","journal-title":"Clin J Gastroenterol"},{"key":"2026062609051570000_16.1.e106630.13","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s12328-020-01272-8","article-title":"The role of oral vancomycin in inducing remission for biologic-experienced ulcerative colitis with concomitant primary sclerosing cholangitis and liver transplantation","volume":"14","author":"Rahman","year":"2021","journal-title":"Clin J Gastroenterol"},{"key":"2026062609051570000_16.1.e106630.14","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1002\/hep.31560","article-title":"Oral Vancomycin, Ursodeoxycholic Acid, or No Therapy for Pediatric Primary Sclerosing Cholangitis: A Matched Analysis","volume":"73","author":"Deneau","year":"2021","journal-title":"Hepatology"},{"key":"2026062609051570000_16.1.e106630.15","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1080\/00365521.2020.1787501","article-title":"Open-label prospective therapeutic clinical trials: oral vancomycin in children and adults with primary sclerosing cholangitis","volume":"55","author":"Ali","year":"2020","journal-title":"Scand J Gastroenterol"},{"key":"2026062609051570000_16.1.e106630.16","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1111\/apt.14586","article-title":"Editorial: vancomycin - a promising option for the treatment of primary sclerosing cholangitis?","volume":"47","author":"Chapman","year":"2018","journal-title":"Aliment Pharmacol Ther"},{"key":"2026062609051570000_16.1.e106630.17","doi-asserted-by":"crossref","unstructured":"Al Mamari S , Djordjevic J , Halliday JS , et al . Improvement of serum alkaline phosphatase to <1.5 upper limit of normal predicts better outcome and reduced risk of cholangiocarcinoma in primary sclerosing cholangitis. J Hepatol 2013;329\u201334.","DOI":"10.1016\/j.jhep.2012.10.013"},{"key":"2026062609051570000_16.1.e106630.18","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz871"},{"key":"2026062609051570000_16.1.e106630.19","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-019-3676-1"},{"key":"2026062609051570000_16.1.e106630.20","doi-asserted-by":"crossref","first-page":"110211","DOI":"10.1016\/j.mehy.2020.110211","article-title":"Long-term oral vancomycin for refractory inflammatory bowel diseases without Clostridium difficile infection: Lessons from primary sclerosing cholangitis","volume":"144","author":"Du","year":"2020","journal-title":"Med Hypotheses"},{"key":"2026062609051570000_16.1.e106630.21","doi-asserted-by":"publisher","DOI":"10.3109\/00365548.2010.544671"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-106630","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T16:05:55Z","timestamp":1782489955000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-106630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,9]]},"published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1136\/bmjopen-2025-106630"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-106630","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]}}}