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

NCT ID: NCT02464020

Last Updated: 2020-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2018-12-01

Brief 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.

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.

Conditions

Primary Sclerosing Cholangitis; Inflammatory Bowel Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

primary sclerosing cholangitis

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

Group Type: EXPERIMENTAL

Vancomycin

Intervention Type: DRUG

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

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Vancomycin

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Byron P Vaughn, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Countries

United States

Other Identifiers

GI-2015-23049

Identifier Type: -

Identifier Source: org_study_id