The Effect of Statin Therapy on Bile Acid Physiology and the Microbiome in Primary Sclerosing Cholangitis (PSC): a Multi-omics Study

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PSC is a liver disease that has no medical cure. Patients with PSC are at a greatly increased risk of cancer and infection. Additionally, many patients require a liver transplant. Progress towards a cure has been severely limited by an incomplete understanding of why patients develop PSC. The investigators aim to close this gap by conducting a pilot human study in patients with PSC, using statin therapy as a model

2023-05-31

2025-05-31

2025-12-31

Recruiting

Early phase I

15

Inclusion Criteria: * Males and females, greater than or equal to 18 years of age * Established diagnosis of PSC, defined by either appropriate cholangiographic findings or supportive liver biopsy plus an established diagnosis of inflammatory bowel disease (IBD - Crohn's disease or ulcerative colitis) per American College of Gastroenterology (ACG) guidelines for the PSC-IBD arm * Hypercholesterolemia with BMI \< 25.0 for the comparison arm Exclusion Criteria: * Diagnosis of PSC-autoimmune hepatitis overlap syndrome * Woman who are pregnant, nursing, or expect to be pregnant * The presence of any comorbidity known to cause secondary sclerosing cholangitis, including: immunoglobulin G-4 (IgG4), associated cholangitis, recurrent bacterial cholangitis, recurrent pyogenic cholangitis, ischemic cholangiopathy, surgical biliary trauma, cholangiocarcinoma, and portal hypertensive biliopathy * Diagnosis of a serious medical condition (unless approved in writing by a physician) * Patients taking statin therapy prior to study initiation * Patients with known clinically allergy to statin therapy * aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 5 times the upper limit of normal * Bilirubin greater than 3.0 mg/dL * Recent use of antibiotics (within the last 90 days) * Concurrent use of any immunosuppressive medications (such as any calcineurin inhibitor, steroids at a dose greater than 10 mg of prednisone-equivalents per day) * Actively using a fibrate drug * Actively using a ritonavir containing drug * Familial hypercholesterolemia or other inherited disorder of lipid metabolism * Recent myocardial infarction or cerebrovascular accident * Body mass index \> 25.0 for the comparison arm * Chronic kidney disease stage 5 or end-stage renal disease

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2024-03-21