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

Обзор

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.

Подробное описание

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

Вмешательства

• Препарат Placebo (blinded)
  Identical placebo capsule administered orally twice daily for 4 weeks.
• Препарат Vancomycin (blinded)
  Vancomycin 250 mg administered orally twice daily for 4 weeks.
• Препарат Vancomycin (open-label extension)
  Vancomycin 250 mg administered orally twice daily for 4 weeks (optional extension offered to both arms).

Первичные конечные точки

• Recruitment rate [Срок оценки: 12 months]
• Retention rate [Срок оценки: 12 months]
• Treatment adherence [Срок оценки: 12 months]
• Protocol compliance with study procedures [Срок оценки: 12 months]

Вторичные конечные точки (4)

• Incidence of adverse events and serious adverse events [Срок оценки: 12 months]
• Severity and type of adverse events [Срок оценки: 12 months]
• Relationship of adverse events to oral vancomycin [Срок оценки: 12 months]
• Patient-reported tolerability of oral vancomycin [Срок оценки: 12 months]

Критерии участия

Критерии включения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• McMaster Children's Hospital - Digestive Diseases Clinic — Hamilton

Публикации

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT07341282 · DRIVE_UP2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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