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

University of Minnesota (UMN)

Status and phase: Completed; Phase 1

Conditions: Primary Sclerosing Cholangitis; Inflammatory Bowel Disease

Treatments: Drug: Vancomycin

Study type: Interventional

Funder types: Other

Identifiers

NCT02464020

GI-2015-23049

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 2 patient groups

primary sclerosing cholangitis

Experimental group

Description:

Two week course of oral vancomycin 500mg twice a day.

Treatment:

Drug: Vancomycin

Control group

No Intervention group

Description:

A control group of participants without Primary Sclerosing Cholangitis. Control group will consist of both healthy subjects and subjects with Inflammatory Bowel Disease.