Statin Therapy in Primary Sclerosing Cholangitis (PSC): a Multi-omics Study

NCT05912387 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 67292
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Primary Sclerosing Cholangitis; Inflammatory Bowel Diseases

Keywords

Statin

Outcome Measures

Primary Outcomes (5)

• Change in bile acid (BA) profile: total bile acid

  BA profile of biliary/intestinal aspirate and/or feces in response to statin therapy.

  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.

  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.

  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.

  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.

  Baseline and week 12

Secondary Outcomes (5)

• Change in bile acid (BA) profile: total bile acid

  Baseline, week 4, week 14

• Change in bile acid (BA) profile: secondary bile acids:primary bile acids ratio

  Baseline, week 4, week 14

• Change in bile acid (BA) profile: conjugated:unconjugated BAs ratio

  Baseline, week 4, week 14

• Change in pathogen density in the small intestine

  Baseline, week 4, week 14

• Change in bacterial gene expression profile in the small intestine

  Baseline, week 4, week 14

Study Arms (1)

Rosuvastatin therapy

EXPERIMENTAL

Participants will receive rosuvastatin for 12 weeks followed by a 2 week washout period prior to the final follow-up visit. All patients will receive the study drug, and will serve as their own control. No participants will receive placebo. Rosuvastatin is FDA approved for treatment of high cholesterol, but its use in this trial is off label.

Drug: Rosuvastatin

Interventions

Rosuvastatin DRUG

Rosuvastatin 20 mg tablet once daily by mouth

Rosuvastatin therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

RECRUITING

MeSH Terms

Conditions

Cholangitis, Sclerosing; Inflammatory Bowel Diseases

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Gastroenteritis; Gastrointestinal Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Sidhartha Sinha, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Touran Fardeen

CONTACT

(650) 725-5890; tfardeen@stanford.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 1, 2023
• First Posted: June 22, 2023
• Study Start: May 31, 2023
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)