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 (

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.

Obstructive sleep apnoea syndrome (OSAS) co-occurs with major depressive disorder (MDD) in approximately 50% of cases, and this comorbidity is associated with greater severity of depressive symptoms, sleep disturbances and poorer clinical outcomes. Although continuous positive airway pressure (CPAP) therapy is effective in treating OSAS and alleviating symptoms of MDD, poor adherence during the initial weeks of treatment remains a major clinical challenge. Bright light therapy has been shown to rapidly improve sleep, wakefulness, cognitive function and mood in patients with MDD. Given these complementary mechanisms, we propose that combining CPAP with bright light therapy may enhance patient adherence during the critical initial phase of CPAP treatment, ultimately leading to better clinical and sleep-related outcomes.

In a single-centre, double-blind, sham-controlled study with two parallel arms, 130 patients with both MDD and OSAS requiring CPAP therapy will be randomly assigned to receive either 14 sessions of 30 min active bright light therapy (n=65, 1200 Lux, peak wavelength at 500 nm) or 14 sessions of 30 min sham bright light therapy (n=65, 33 Lux, peak wavelength at 600 nm) during the first 2 weeks, following CPAP initiation at home. The primary outcome will be adherence to CPAP (in hours per 24 hours during the 14 days of investigation). Secondary clinical outcomes will include changes in depressive and anxiety symptoms. Secondary sleep-related outcomes will include both objective sleep parameters (polysomnography, melatonin and actimetry) and standardised psychometric scales. The persistence of treatment effects at 1-month follow-up will also be evaluated.

The study was approved by an ethics committee (CPP Nord Ouest IV, Lille, France), and the French National Agency for Medicines and Health Products Safety registration number 2024-A01551-46. The findings will be disseminated through international peer-reviewed publications, presentations at scientific conferences and outreach at public conferences.

NCT06781593.