A Pilot Study to Characterize Bile Acid Metabolism and Dysbiosis in Primary Sclerosing Cholangitis
| Status: | Completed |
|---|---|
| Conditions: | Irritable Bowel Syndrome (IBS), Gastrointestinal, Gastrointestinal |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 4/3/2019 |
| Start Date: | July 2015 |
| End Date: | December 1, 2018 |
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.
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.
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.
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.
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
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