Investigation of Vancomycin Efficacy in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis

This is an investigator-initiated feasibility study designed to rigorously characterize clinical response signals, safety parameters, and feasibility metrics in adults with co-existing PSC and UC, a population where microbiome-targeted immune modulation is hypothesized to influence disease activity. Randomization \& Allocation Governance * Randomization will be implemented using validated computer-generated randomization software, with the allocation sequence generated by a study statistician not involved in clinical assessments. * Allocation concealment will be maintained through centralized pharmacy control. An independent pharmacist will assign treatment codes and release sequentially numbered study medication containers. * Blinding integrity will be preserved through visual and packaging equivalence, sequential drug accountability logs, and restricted access to treatment codes until database lock. * Emergency unblinding is permitted only when required for clinical management, and all unblinding events will be documented, timestamped, and reviewed by the DSMC. Clinical Visit \& Assessment Schedule Participants will complete a structured study visit pathway: * Screening (≤14 days before baseline): medical history review, infection risk screening, liver disease stability assessment, and confirmation of clinical trial eligibility documentation. * Baseline (Week 0): clinical evaluation, safety labs, medication reconciliation, and flexible sigmoidoscopy performed by credentialed endoscopists using a standardized endoscopic scoring handbook. * Week 2 \& 4: in-clinic evaluation, adverse event review, safety labs, and compliance verification via pill count and participant diary reconciliation. * Week 8 (extension follow-up): final safety labs, medication reconciliation, delayed adverse event capture, and optional qualitative feasibility interview. Adherence \& Safety Surveillance * Participants will complete weekly digital symptom and adherence diaries capturing stool frequency, rectal bleeding trends, abdominal pain patterns, and missed doses. * Safety labs include CBC, creatinine, liver panel, CRP, albumin, electrolytes, and will be evaluated at baseline, week 2, 4, and 8. * A hepatologist co-investigator will review liver safety signals in real-time, given PSC-specific vulnerability to hepatic decompensation. * Audiology risk is screened at entry, and any symptoms concerning for ototoxicity will prompt same-week clinical review. Data Capture \& Monitoring Integrity * All data will be captured in a secure Excel file * Endoscopic images will be stored in a secured institutional imaging server. * A pre-registered statistical analysis plan will be finalized before unblinding, with analysis scripts locked prior to treatment code release. Safety Governance Structure The DSMC will provide independent oversight and safety adjudication: * Quarterly DSMC meetings will evaluate cumulative safety logs, recruitment feasibility, protocol deviations, and unblinding reports. * A real-time SAE notification system ensures DSMC alert within 24 hours of serious adverse event reporting. * Pre-defined individual, arm-level, and whole-trial safety review thresholds are codified in the DSMC governance charter to support early pause or protocol modification when required. Regulatory \& Ethical Compliance The trial will follow all institutional and international regulatory standards: * ICH-GCP * Institutional Research Ethics Board approval * DSMC governance charter * GMP-aligned pharmacy accountability procedures