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

Inflammatory Bowel Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02464020
• Other study ID #: GI-2015-23049
• Status: Completed
• Phase: Phase 1
• Start date: July 2015
• Est. completion date: December 1, 2018

Study information

• Verified date: July 2020
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: December 1, 2018
• Est. primary completion date: May 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Dysbiosis
• Inflammatory Bowel Disease
• Inflammatory Bowel Diseases
• Primary Sclerosing Cholangitis

Intervention

Drug:
• Vancomycin
Oral vancomycin: 500mg suspended in prefilled syringes for oral use

Locations

Country	Name	City	State
United States	University of Minnesota Medical Center	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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