Clinical trial NCT02464020: A Pilot Study to Characterize Bile Acid Metabolism and Dysbiosis in Primary Sclerosing Cholangitis
Official title: A Pilot Study to Characterize Bile Acid Metabolism and Dysbiosis in Primary Sclerosing Cholangitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Primary Sclerosing Cholangitis
Inflammatory Bowel Disease
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2015-06-08
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Fecal bile acid composition
timeFrame: 5 days
Secondary outcomes:
measure: Microbiome diversity analysis
timeFrame: 5 days
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Byron P Vaughn, MD
role: PRINCIPAL_INVESTIGATOR
References: