search
Back to results

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

Primary Purpose

Primary Sclerosing Cholangitis, Inflammatory Bowel Diseases

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Rosuvastatin
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Primary Sclerosing Cholangitis focused on measuring Statin

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Stanford UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rosuvastatin therapy

Arm Description

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.

Outcomes

Primary Outcome Measures

Change in bile acid (BA) profile: total bile acid
BA profile of biliary aspirate and feces in response to statin therapy.
Change in bile acid (BA) profile: secondary bile acids:primary bile acids ratio
BA profile of biliary aspirate and feces in response to statin therapy.
Change in bile acid (BA) profile: conjugated:unconjugated BAs ratio
BA profile of biliary aspirate and feces in response to statin therapy.
Change in pathogen density in the duodenum
Measure impact of statin therapy upon pathogen density (ratio of good bacteria to pathogenic bacteria) within the microbial community of the duodenum.
Change in bacterial gene expression profile in the duodenum
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.

Secondary Outcome Measures

Change in bile acid (BA) profile: total bile acid
BA profile of biliary aspirate and feces in response to statin therapy.
Change in bile acid (BA) profile: secondary bile acids:primary bile acids ratio
BA profile of biliary aspirate and feces in response to statin therapy.
Change in bile acid (BA) profile: conjugated:unconjugated BAs ratio
BA profile of biliary aspirate and feces in response to statin therapy.
Change in pathogen density in the duodenum
Measure impact of statin therapy upon pathogen density (ratio of good bacteria to pathogenic bacteria) within the microbial community of the duodenum.
Change in bacterial gene expression profile in the duodenum
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.

Full Information

First Posted
June 1, 2023
Last Updated
June 12, 2023
Sponsor
Stanford University
search

1. Study Identification

Unique Protocol Identification Number
NCT05912387
Brief Title
Statin Therapy in Primary Sclerosing Cholangitis (PSC): a Multi-omics Study
Official Title
The Effect of Statin Therapy on Bile Acid Physiology and the Microbiome in Primary Sclerosing Cholangitis (PSC): a Multi-omics Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 31, 2023 (Actual)
Primary Completion Date
May 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sclerosing Cholangitis, Inflammatory Bowel Diseases
Keywords
Statin

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Rosuvastatin therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Rosuvastatin
Intervention Description
Rosuvastatin 20 mg tablet once daily by mouth
Primary Outcome Measure Information:
Title
Change in bile acid (BA) profile: total bile acid
Description
BA profile of biliary aspirate and feces in response to statin therapy.
Time Frame
Baseline and week 12
Title
Change in bile acid (BA) profile: secondary bile acids:primary bile acids ratio
Description
BA profile of biliary aspirate and feces in response to statin therapy.
Time Frame
Baseline and week 12
Title
Change in bile acid (BA) profile: conjugated:unconjugated BAs ratio
Description
BA profile of biliary aspirate and feces in response to statin therapy.
Time Frame
Baseline and week 12
Title
Change in pathogen density in the duodenum
Description
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
Title
Change in bacterial gene expression profile in the duodenum
Description
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
Secondary Outcome Measure Information:
Title
Change in bile acid (BA) profile: total bile acid
Description
BA profile of biliary aspirate and feces in response to statin therapy.
Time Frame
Baseline, week 4, week 14
Title
Change in bile acid (BA) profile: secondary bile acids:primary bile acids ratio
Description
BA profile of biliary aspirate and feces in response to statin therapy.
Time Frame
Baseline, week 4, week 14
Title
Change in bile acid (BA) profile: conjugated:unconjugated BAs ratio
Description
BA profile of biliary aspirate and feces in response to statin therapy.
Time Frame
Baseline, week 4, week 14
Title
Change in pathogen density in the duodenum
Description
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
Title
Change in bacterial gene expression profile in the duodenum
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Touran Fardeen
Phone
(650) 725-5890
Email
tfardeen@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chiraag Kulkarni, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Touran Fardeen
Email
tfardeen@stanford.edu

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Individual participant data will not be shared

Learn more about this trial

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

We'll reach out to this number within 24 hrs