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

NCT07341282 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: DRIVE_UP2025
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ulcerative Colitis (UC); Primary Sclerosing Cholangitis (PSC)

Keywords

Ulcerative Colitis; Primary Sclerosing Cholangitis; Vancomycin; Randomized Control Trial

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• Incidence of adverse events and serious adverse events

  12 months

• Severity and type of adverse events

  12 months

• Relationship of adverse events to oral vancomycin

  12 months

• Patient-reported tolerability of oral vancomycin

  12 months

Other Outcomes (5)

• Exploratory Endpoints (Change in Mayo Score from baseline)

  12 months

• Exploratory Endpoints (Change in serum liver enzymes from baseline)

  12 months

• Exploratory Endpoints (Change in gut microbiome diversity from baseline)

  12 months

Study Arms (2)

Placebo Comparator

PLACEBO COMPARATOR

4 weeks blinded placebo followed by optional 4 weeks open-label vancomycin.

Drug: Placebo (blinded); Drug: Vancomycin (open-label extension)

Vancomycin

EXPERIMENTAL

4 weeks blinded oral vancomycin followed by optional additional 4 weeks open-label vancomycin.

Drug: Vancomycin (blinded); Drug: Vancomycin (open-label extension)

Interventions

Placebo (blinded) DRUG

Identical placebo capsule administered orally twice daily for 4 weeks.

Placebo Comparator

Vancomycin (blinded) DRUG

Vancomycin 250 mg administered orally twice daily for 4 weeks.

Vancomycin

Vancomycin (open-label extension) DRUG

Vancomycin 250 mg administered orally twice daily for 4 weeks (optional extension offered to both arms).

Placebo Comparator; Vancomycin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged ≥18 years.
• Confirmed diagnosis of UC and PSC.
• Moderate to severe UC disease activity (total Mayo score ≥5; endoscopic subscore ≥2).

You may not qualify if:

• 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

Sponsors & Collaborators

• McMaster University: lead
• Weston Family Foundation: collaborator

Study Sites (1)

McMaster Children's Hospital - Digestive Diseases Clinic

Hamilton, Ontario, L8N 3Z5, Canada

Location

Related Publications (9)

• 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.

  PMID: 39495039 BACKGROUND

• 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.

  PMID: 32250997 BACKGROUND

• 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.

  PMID: 40002259 BACKGROUND

• 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.

  PMID: 24612141 BACKGROUND

• 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.

  PMID: 23448792 BACKGROUND

• 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.

  PMID: 34357546 BACKGROUND

• 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.

  PMID: 21363920 BACKGROUND

• Ullman TA, Itzkowitz SH. Intestinal inflammation and cancer. Gastroenterology. 2011 May;140(6):1807-16. doi: 10.1053/j.gastro.2011.01.057.

  PMID: 21530747 BACKGROUND

• 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.

  PMID: 34584578 BACKGROUND

MeSH Terms

Conditions

Colitis, Ulcerative; Cholangitis, Sclerosing

Interventions

Vancomycin

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases; Cholangitis; Bile Duct Diseases; Biliary Tract Diseases

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Neeraj Narula, MD

  McMaster University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Neeraj Narula, MD

CONTACT

905-521-2100; neeraj.narula@medportal.ca

Jaimin Patel

CONTACT

905-521-2100; patej102@mcmaster.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will: Be randomized to receive either vancomycin or placebo orally twice daily for 4 weeks. Undergo clinical assessments including Mayo scoring, endoscopic evaluation, and laboratory testing at baseline, week 4, and follow-up. After 4 weeks, have the option to receive open-label vancomycin for an additional 4 weeks. Provide stool and blood samples for microbiome and biochemical analyses. Be monitored for adverse events and treatment adherence throughout the trial.

Study Record Dates

• First Submitted: December 2, 2025
• First Posted: January 14, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: January 14, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Start Date is estimated in January 2026 - end date is estimated in December 2026.
• 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.

Locations

CA (1)