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.

Abstract

Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). No therapy currently halts disease progression. The strong gut-liver 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. 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 15-75 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 mg/day or OV 1500 mg/day for 24 weeks. Randomisation will be stratified by baseline liver stiffness (< or ≥14.4 kPa). Participants will be followed at 4 and 12 weeks post-treatment. The primary efficacy outcome is the change in serum alkaline phosphatase at 24 weeks. 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. The protocol has been approved by the Ethics Committee CE Brianza on 10 February 2023, number 4017. Trial registration number NCT05876182. 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. NCT05876182.