Statin Therapy in Primary Sclerosing Cholangitis (PSC): a Multi-omics Study
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Rosuvastatin.
- Who it may be relevant to
- Registry conditions: Primary Sclerosing Cholangitis, Inflammatory Bowel Diseases. Basic parameters: 18 years — 80 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
The Effect of Statin Therapy on Bile Acid Physiology and the Microbiome in Primary Sclerosing Cholangitis (PSC): a Multi-omics Study
Overview
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
Detailed description
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.
Interventions
- Drug Rosuvastatin
Rosuvastatin 20 mg tablet once daily by mouth
Primary outcome measures
- Change in bile acid (BA) profile: total bile acid [Time frame: Baseline and week 12]
- Change in bile acid (BA) profile: secondary bile acids:primary bile acids ratio [Time frame: Baseline and week 12]
- Change in bile acid (BA) profile: conjugated:unconjugated BAs ratio [Time frame: Baseline and week 12]
- Change in pathogen density in the small intestine [Time frame: Baseline and week 12]
- Change in bacterial gene expression profile in the small intestine [Time frame: Baseline and week 12]
Secondary outcome measures (5)
- Change in bile acid (BA) profile: total bile acid [Time frame: Baseline, week 4, week 14]
- Change in bile acid (BA) profile: secondary bile acids:primary bile acids ratio [Time frame: Baseline, week 4, week 14]
- Change in bile acid (BA) profile: conjugated:unconjugated BAs ratio [Time frame: Baseline, week 4, week 14]
- Change in pathogen density in the small intestine [Time frame: Baseline, week 4, week 14]
- Change in bacterial gene expression profile in the small intestine [Time frame: Baseline, week 4, week 14]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Basic science
Study locations
United States · 1 center
- Stanford University — Stanford
Identifiers
NCT: NCT05912387 · 67292