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
Database studies have suggested that use of statins is associated with lower mortality in patients with PSC. Statins are also safe, widely used medications for the treatment of high cholesterol. This track record of safety makes repurposing statins for use in PSC an attractive option. This study will evaluate the impact of bile acid profile and the microbiome. Rosuvastatin induced changes in cell signaling pathways in the body, as well as its impact of bacterial gene expression in the microbiome will be evaluated. The investigators anticipate that this study will provide key insights into the biologic basis of PSC, which may aid in the development of drugs for the treatment of PSC. This research study will enroll patients with PSC. The study will be conducted in 3 phases: baseline measurements, study period (treatment with rosuvastatin), and follow-up (follow-up after completing statin treatment). All patients will receive the study drug, and no patients will receive placebo treatment. Rosuvastatin is FDA approved for treatment of high cholesterol, but its use in this trial is off label.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
15
Rosuvastatin 20 mg tablet once daily by mouth
Stanford University
Stanford, California, United States
RECRUITINGChange in bile acid (BA) profile: total bile acid
BA profile of biliary/intestinal aspirate and/or feces in response to statin therapy.
Time frame: Baseline and week 12
Change in bile acid (BA) profile: secondary bile acids:primary bile acids ratio
BA profile of biliary/intestinal aspirate and/or feces in response to statin therapy.
Time frame: Baseline and week 12
Change in bile acid (BA) profile: conjugated:unconjugated BAs ratio
BA profile of biliary/intestinal aspirate and/or feces in response to statin therapy.
Time frame: Baseline and week 12
Change in pathogen density in the small intestine
Measure impact of statin therapy upon pathogen density (ratio of good bacteria to pathogenic bacteria) within the microbial community of the duodenum.
Time frame: Baseline and week 12
Change in bacterial gene expression profile in the small intestine
This outcome aims to develop an understanding of the profile of microbial metabolic pathways in the duodenum and changes to the profile in response to statin therapy; gene sequencing with be done using shotgun metagenomics followed by pathway analysis.
Time frame: Baseline and week 12
Change in bile acid (BA) profile: total bile acid
BA profile of biliary/intestinal aspirate and/or feces in response to statin therapy.
Time frame: Baseline, week 4, week 14
Change in bile acid (BA) profile: secondary bile acids:primary bile acids ratio
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BA profile of biliary/intestinal aspirate and/or feces in response to statin therapy.
Time frame: Baseline, week 4, week 14
Change in bile acid (BA) profile: conjugated:unconjugated BAs ratio
BA profile of biliary/intestinal aspirate and/or feces in response to statin therapy.
Time frame: Baseline, week 4, week 14
Change in pathogen density in the small intestine
Measure impact of statin therapy upon pathogen density (ratio of good bacteria to pathogenic bacteria) within the microbial community of the duodenum.
Time frame: Baseline, week 4, week 14
Change in bacterial gene expression profile in the small intestine
This outcome aims to develop an understanding of the profile of microbial metabolic pathways in the duodenum and changes to the profile in response to statin therapy; gene sequencing with be done using shotgun metagenomics followed by pathway analysis.
Time frame: Baseline, week 4, week 14