Investigation of Vancomycin Efficacy in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis (DRIVE-UP)

This clinical trial tests if oral vancomycin can safely treat active ulcerative colitis (UC) in adults who also have primary sclerosing cholangitis (PSC), a liver condition. The main questions it aims to answer are:

• Can oral vancomycin improve UC symptoms as measured by Mayo score at 4 weeks?
• Is oral vancomycin safe and tolerable in this patient group?

Participants will be compared to see if vancomycin works better than placebo. Participants will:

• Take oral vancomycin (250 mg twice daily) or identical placebo capsules for 4 weeks
• Have the option for 4 more weeks of open-label vancomycin after the blinded phase
• Attend clinic visits at baseline, week 4, and follow-up for Mayo scoring, endoscopy, blood/stool tests, and safety checks
• Track treatment adherence and side effects

The study primarily assesses if the trial can recruit 14 participants, retain them, achieve good adherence, and follow protocol procedures (feasibility). Secondary goals include safety (adverse events) and early signs of benefit in UC activity, liver tests, and gut bacteria balance. This pilot will guide larger future studies.

Study Overview

• Status: Not yet recruiting
• Conditions: Primary Sclerosing Cholangitis (PSC); Ulcerative Colitis (UC)
• Intervention / Treatment: Drug: Placebo (blinded); Drug: Vancomycin (open-label extension); Drug: Vancomycin (blinded)

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Neeraj Narula, MD; Phone Number: 73884 905-521-2100; Email: neeraj.narula@medportal.ca
• Study Contact Backup: Name: Jaimin Patel; Phone Number: 73884 905-521-2100; Email: patej102@mcmaster.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster Children's Hospital - Digestive Diseases Clinic
      • Contact: Neeraj Narula, MD; Phone Number: 73884 905-521-2100; Email: neeraj.narula@medportal.ca
      • Principal Investigator: Neeraj Narula, MD
      • Contact: Jaimin Patel; Phone Number: 73884 905-521-2100; Email: patej102@mcmaster.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Comparator; 4 weeks blinded placebo followed by optional 4 weeks open-label vancomycin.	Drug: Placebo (blinded); Identical placebo capsule administered orally twice daily for 4 weeks.; Drug: Vancomycin (open-label extension); Vancomycin 250 mg administered orally twice daily for 4 weeks (optional extension offered to both arms).
Experimental: Vancomycin; 4 weeks blinded oral vancomycin followed by optional additional 4 weeks open-label vancomycin.	Drug: Vancomycin (open-label extension); Vancomycin 250 mg administered orally twice daily for 4 weeks (optional extension offered to both arms).; Drug: Vancomycin (blinded); Vancomycin 250 mg administered orally twice daily for 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rate	Proportion of eligible participants who provide consent and are enrolled in the study (number enrolled ÷ number eligible approached), with a target of 14 participants within 12 months.	12 months
Retention rate	Proportion of enrolled participants who complete all protocol-specified study visits and assessments at 12 months (number completing all follow-up visits ÷ number enrolled).	12 months
Treatment adherence	Proportion of prescribed oral vancomycin doses taken over the treatment period, assessed by pill counts and/or medication diary (number of doses taken ÷ number of doses prescribed).	12 months
Protocol compliance with study procedures	Proportion of participants with all required visits, laboratory tests, and assessments completed per protocol (number fully compliant ÷ number enrolled); may also include rate of major protocol deviations.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events and serious adverse events	Proportion of participants with at least one treatment-emergent adverse event (AE) or serious adverse event (SAE)	12 months
Severity and type of adverse events	Number of treatment-emergent AEs and SAEs by maximum severity grade (mild/moderate/severe) and type (MedDRA preferred term).	12 months
Relationship of adverse events to oral vancomycin	Proportion of AEs/SAEs assessed by investigator as related to intervention (number related ÷ total events).	12 months
Patient-reported tolerability of oral vancomycin	Mean score of side effect frequency and impact on 0-10 scale (0=no impact, 10=worst impact) via study questionnaire.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Endpoints (Change in Mayo Score from baseline)	Change in partial Mayo Clinic Score (range 0-12 points, higher scores indicate greater ulcerative colitis disease activity) from baseline to 12 months.	12 months
Exploratory Endpoints (Change in serum liver enzymes from baseline)	Change in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (units: U/L) from baseline to 12 months.	12 months
Exploratory Endpoints (Change in gut microbiome diversity from baseline)	Change in gut microbiome diversity (Shannon index, unitless) measured by 16S rRNA sequencing of fecal samples from baseline to 12 months.	12 months
Exploratory Endpoints (Change in fecal bile acids from baseline)	Change in total fecal bile acid concentration (units: μmol/g) measured by mass spectrometry from baseline to 12 months.	12 months
Exploratory Endpoints (Change in fecal short chain fatty acids from baseline)	Change in total fecal short chain fatty acid concentration (units: μmol/g), including acetate, propionate, and butyrate, measured by gas chromatography from baseline to 12 months.	12 months

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Weston Family Foundation
• Investigators: Principal Investigator: Neeraj Narula, MD, McMaster University

Publications and helpful links

General Publications

• Ullman TA, Itzkowitz SH. Intestinal inflammation and cancer. Gastroenterology. 2011 May;140(6):1807-16. doi: 10.1053/j.gastro.2011.01.057.
• Arbabzada N, Dennett L, Meng G, Peerani F. The Effectiveness of Oral Vancomycin on Inflammatory Bowel Disease in Patients With Primary Sclerosing Cholangitis: A Systematic Review. Inflamm Bowel Dis. 2025 Jul 7;31(7):2027-2035. doi: 10.1093/ibd/izae257.
• Shah A, Macdonald GA, Morrison M, Holtmann G. Targeting the Gut Microbiome as a Treatment for Primary Sclerosing Cholangitis: A Conceptional Framework. Am J Gastroenterol. 2020 Jun;115(6):814-822. doi: 10.14309/ajg.0000000000000604.
• Al Sulais E, AlAmeel T, Alenzi M, Shehab M, AlMutairdi A, Al-Bawardy B. Colorectal Neoplasia in Inflammatory Bowel Disease. Cancers (Basel). 2025 Feb 16;17(4):665. doi: 10.3390/cancers17040665.
• Castano-Milla C, Chaparro M, Gisbert JP. Systematic review with meta-analysis: the declining risk of colorectal cancer in ulcerative colitis. Aliment Pharmacol Ther. 2014 Apr;39(7):645-59. doi: 10.1111/apt.12651.
• Lutgens MW, van Oijen MG, van der Heijden GJ, Vleggaar FP, Siersema PD, Oldenburg B. Declining risk of colorectal cancer in inflammatory bowel disease: an updated meta-analysis of population-based cohort studies. Inflamm Bowel Dis. 2013 Mar-Apr;19(4):789-99. doi: 10.1097/MIB.0b013e31828029c0.
• Lundberg Bave A, Bergquist A, Bottai M, Warnqvist A, von Seth E, Nordenvall C. Increased risk of cancer in patients with primary sclerosing cholangitis. Hepatol Int. 2021 Oct;15(5):1174-1182. doi: 10.1007/s12072-021-10214-6. Epub 2021 Aug 6.
• Risques RA, Lai LA, Himmetoglu C, Ebaee A, Li L, Feng Z, Bronner MP, Al-Lahham B, Kowdley KV, Lindor KD, Rabinovitch PS, Brentnall TA. Ulcerative colitis-associated colorectal cancer arises in a field of short telomeres, senescence, and inflammation. Cancer Res. 2011 Mar 1;71(5):1669-79. doi: 10.1158/0008-5472.CAN-10-1966.
• Uzdzicki AW, Wawrzynowicz-Syczewska M. Characteristic features of ulcerative colitis with concomitant primary sclerosing cholangitis. Prz Gastroenterol. 2021;16(3):184-187. doi: 10.5114/pg.2021.108983. Epub 2021 Sep 17.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: January 5, 2026
• First Posted (Actual): January 14, 2026

Study Record Updates

• Last Update Posted (Actual): January 14, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Vancomycin; Ulcerative Colitis; Randomized Control Trial; Primary Sclerosing Cholangitis
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Biliary Tract Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Bile Duct Diseases; Colitis; Cholangitis; Colitis, Ulcerative; Cholangitis, Sclerosing; Peptides; Amino Acids, Peptides, and Proteins; Carbohydrates; Glycoconjugates; Glycopeptides; Vancomycin
• Other Study ID Numbers: DRIVE_UP2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data sharing policies would follow institutional and regulatory standards on data confidentiality and sharing.

De-identified data shared upon request to qualified researchers with appropriate data use agreements, respecting participant confidentiality and ethical approvals.

Patient demographics, primary data and data analysis can be shared.

• IPD Sharing Time Frame: Start Date is estimated in January 2026 - end date is estimated in December 2026.

IPD Sharing Access Criteria

Access to IPD and supporting study documents will generally limited to qualified researchers who submit a reasonable scientific request and have the necessary expertise.

The data shared would be de-identified or anonymized to protect participant confidentiality.

Researchers might be granted access under data use agreements that specify the terms of use, including restrictions on re-identification and further sharing.

Access is often facilitated through secure data repositories or by request through the trial sponsor or coordinating research unit after review and approval of the request.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No