Clinical trial NCT01802073: Primary Sclerosing Cholangitis With Oral Vancomycin by the Study of Its Antimicrobial and Immunomodulating Effects
Official title: Treatment of Primary Sclerosing Cholangitis in Inflammatory Bowel Disease Patients With Oral Vancomycin by the Study of Its Antimicrobial and Immunomodulating Effects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Sclerosing Cholangitis
Keywords: Inflammation of the bile ducts
biliary scarring
obstruction
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2013-03-01
Enrollment: 34
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Determine the benefit of oral vancomycin therapy for Primary Sclerosing Cholangitis.

Detailed description: The purpose of this study is to evaluate changes in the fecal and salivary/urinary microbiota during vancomycin treatment of children and adults with Primary Sclerosing Cholangitis (PSC), identify features of the host microbiota that are associated with disease activity and/or response to treatment and further delineate the immunological effects of oral vancomycin treatment of PSC. This study will correlate changes in microbiota with the immunological effects of oral vancomycin in children and adults with PSC. The results of this proposal will lead to new and validated targets for diagnosis and treatment of PSC that will have high impact in the short and long term for patients and their families.

Interim results were published in Abarbanel et al, J Clin Immunol 2013 (see References).

Eligibility criteria: Inclusion Criteria:

* PSC Diagnosis: Liver biopsy and/or imaging (MRCP, ERCP, CT, or US
* Colonoscopy within 1 year or starting of study
* 2 groups:

  1. IBD (Inflammatory bowel disease) and PSC: details of extent and type of IBD
  2. No IBD and PSC, but positive p-ANCA or ASCA serologies indicating possible IBD.

Exclusion Criteria:

* Allergy to Vancomycin
* PSC not associated with IBD or NO positive IBD antibodies (p-ANCA \[anti- neutrophil cytoplasmic antibody\] or ASCA \[anti-Saccharomyces cerevisiae antibody\])
* Cholangiocarcinoma
* On oral or topical (enemas or suppositories) corticosteroids,topical mesalamine, or biologics (infliximab, adalimumab, certolizumab).

Primary outcomes:
measure: Count of Participants With Elevated Alanine Aminotransferase (ALT) at Baseline and With Clinically Significant Improvement at Month 3
timeFrame: Baseline; Month 3
measure: Count of Participants With Elevated Gamma-glutamyltransferase (GGT) at Baseline and With Clinically Significant Improvement at Month 3
timeFrame: Baseline; Month 3
measure: Count of Participants With Elevated ALT and/or GGT at Baseline and With Clinically Significant Improvement at Month 3
timeFrame: Baseline; Month 3
measure: Count of Participants With Abnormal Magnetic Resonance Cholangiopancreatography (MRCP) Imaging at Baseline and With Clinically Significant Improvement at Year 1
timeFrame: Baseline; Year 1
measure: Count of Participants With Abnormal Liver Biopsies at Baseline and With Clinically Significant Improvement at Year 1
timeFrame: Baseline; Year 1
measure: Count of Participants With Abnormal MRCP and/or Liver Biopsy at Baseline and With Clinically Significant Improvement at Year 1
timeFrame: Baseline; Year 1
Secondary outcomes:
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
Study officials:
affiliation: Stanford University
name: Kenneth Cox, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Abarbanel DN, Seki SM, Davies Y, Marlen N, Benavides JA, Cox K, Nadeau KC, Cox KL. Immunomodulatory effect of vancomycin on Treg in pediatric inflammatory bowel disease and primary sclerosing cholangitis. J Clin Immunol. 2013 Feb;33(2):397-406. doi: 10.1007/s10875-012-9801-1. Epub 2012 Oct 9.
citation: Ali AH, Damman J, Shah SB, Davies Y, Hurwitz M, Stephen M, Lemos LM, Carey EJ, Lindor KD, Buness CW, Alrabadi L, Berquist WE, Cox KL. Open-label prospective therapeutic clinical trials: oral vancomycin in children and adults with primary sclerosing cholangitis. Scand J Gastroenterol. 2020 Aug;55(8):941-950. doi: 10.1080/00365521.2020.1787501. Epub 2020 Jul 7.