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

Sponsor

University of Minnesota (Other)

Overall Status

Completed

CT.gov ID

NCT02464020

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Sclerosing Cholangitis Inflammatory Bowel Disease	Drug: Vancomycin	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Jul 1, 2015

Actual Primary Completion Date :

May 1, 2017

Actual Study Completion Date :

Dec 1, 2018

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Fecal bile acid composition [5 days]
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

Secondary Outcome Measures

Microbiome diversity analysis [5 days]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Minnesota Medical Center	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

University of Minnesota

Investigators

Principal Investigator: Byron P Vaughn, MD, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University of Minnesota

ClinicalTrials.gov Identifier:

NCT02464020

Other Study ID Numbers:

GI-2015-23049

First Posted:

Jun 8, 2015

Last Update Posted:

Jul 17, 2020

Last Verified:

Jul 1, 2020

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Inflammatory Bowel Diseases

Cholangitis

Cholangitis, Sclerosing

Dysbiosis

Vancomycin

Study Results

No Results Posted as of Jul 17, 2020