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

Inclusion criteria

• Adults aged ≥18 years.
• Confirmed diagnosis of UC and PSC.
• Moderate to severe UC disease activity (total Mayo score ≥5; endoscopic subscore ≥2).
• Informed consent provided. Exclusion Criteria
• Diagnosis of Crohn's disease or indeterminate colitis.
• Fulminant colitis or need for immediate surgical intervention.
• Use of antibiotics or probiotics within the past 4 weeks (for microbiome substudy).
• Decompensated liver disease (Child-Pugh B/C).
• Severe Renal Impairment (CrCl <30mL/min)
• Active untreated infection.
• Pregnancy or lactation.
• Prior allergy or intolerance to Vancomycin
• History of hearing loss or current hearing problems