A Pilot Study to Characterize Bile Acid Metabolism and Dysbiosis in Primary Sclerosing Cholangitis

The goal of this study is to assess if oral vancomycin can restore the normal bile acid metabolism of people with Primary Sclerosing Cholangitis and Inflammatory Bowel Disease. Study participants will provide blood and stool samples in order to evaluate the bile acid metabolism before a short course of vancomycin and then again after to assess for change. The investigators will also assess the blood and stool of healthy people, and people with IBD (without PSC) as a control group.

Study Overview

• Status: Completed
• Conditions: Primary Sclerosing Cholangitis; Inflammatory Bowel Disease
• Intervention / Treatment: Drug: Vancomycin

Detailed Description

Primary Sclerosing Cholangitis (PSC) is a chronic inflammatory and fibrotic disease of the intra and extrahepatic ducts of unknown etiology that predominately occurs in people with Inflammatory Bowel Disease (IBD). One hypothesis is that altered microbiome (bacteria in the gut) in people with IBD are responsible for the inflammation in the liver seen in PSC. Bile acids (BAs) represent a unique mechanism of communication between the host and intestinal microbiome and the liver. Synthesized in the liver, bile acids are metabolized by intestinal bacteria hydroxylases to secondary BAs which then re-enter the portal circulation. Altered metabolism of BAs has been associated with gallstones and colorectal cancer and is hypothesized to play a role in the inflammatory response of certain disease such as IBD and PSC.

IBD has been associated with impairment of bile acid (BA) metabolism. In addition BAs play a role in regulating bacterial growth of the intestine and thus have an effect on the integrity of the intestinal mucosa, which is an essential component of IBD. Perturbations in this system could increase bacterial translocation into the portal system due to loss of protective mucosal factors or bacterial overgrowth.

The overall goal of this study is to assess the changes in BAs metabolism following administration of oral vancomycin. The investigators will also describe the relationship of the intestinal microbiome and BA metabolism in PSC/IBD.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University Of Minnesota Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documented diagnosis of PSC made by typical clinical, radiographic and biochemical criteria.
• Diagnosis of PSC > 3 months

Exclusion Criteria:

• Antibiotic use within 30 days of initial study visit
• Probiotic use within 30 days of initial study visit
• Extensive ileal disease
• Severe of fulminant IBD
• Diabetes and/or metabolic syndrome
• Chronic disease state deemed unacceptable for the study per investigator review
• Decompensated Cirrhosis
• Females who are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: primary sclerosing cholangitis; Two week course of oral vancomycin 500mg twice a day.	Drug: Vancomycin; Oral vancomycin: 500mg suspended in prefilled syringes for oral use
No Intervention: Control group; A control group of participants without Primary Sclerosing Cholangitis. Control group will consist of both healthy subjects and subjects with Inflammatory Bowel Disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal bile acid composition	Fecal samples will be collected over 1 week. Bile acids will be measured on each sample and the average composition of primary to secondary bile acids over the 5 day period will be assessed. Comparison will be made pre and post vancomycin	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiome diversity analysis	Fecal samples collected over the course of a week will be assessed by 16S r-Ribosomal Ribonucleic Acid gene profiling. Intestinal microbial communities will be assessed pre and post vancomycin administration.	5 days

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Byron P Vaughn, MD, University Of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: May 29, 2015
• First Submitted That Met QC Criteria: June 2, 2015
• First Posted (Estimate): June 8, 2015

Study Record Updates

• Last Update Posted (Actual): July 17, 2020
• Last Update Submitted That Met QC Criteria: July 15, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Biliary Tract Diseases; Bile Duct Diseases; Inflammatory Bowel Diseases; Cholangitis; Cholangitis, Sclerosing; Dysbiosis; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: GI-2015-23049

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No