Pharmacologic Approaches to Preventing Primary Sclerosing Cholangitis Recurrence After Liver Transplantation

NCT06905054 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 24-007598
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to determine the efficacy of 36 months once-daily fenofibrate in preventing clinically-detectable recurrence of primary sclerosing cholangitis after liver transplantation, compared with a historical control cohort that was not treated with

Conditions

Primary Sclerosing Cholangitis; Liver Transplant, Complications; PSC; Biliary Strictures

Keywords

primary sclerosing cholangitis; recurrent primary sclerosing cholangitis; liver transplant complication; fenofibrate; fibrate; PPAR agonist; peroxisome proliferated activated receptor agonist

Outcome Measures

Primary Outcomes (1)

• To determine the incidence of rPSC in LT recipients treated with fenofibrate, compared with an untreated control cohort.

  Proportion of recipients transplanted for PSC who develop rPSC during a 36-month fenofibrate treatment period, compared to the rate of rPSC in a untreated cohort. The diagnosis of rPSC will be made based on established diagnostic criteria (see Study Design)

  36 months

Secondary Outcomes (6)

• To quantify the associations between serum alkaline phosphatase and rPSC development in LT recipients treated with fenofibrate

  36 months

• To quantify the associations between total serum bile acid level and rPSC development in LT recipients treated with fenofibrate

  36 months

• To quantify the associations between serum bile acid profile and rPSC development in LT recipients treated with fenofibrate

  36 months

• To quantify the associations between fibroblast growth factor 19 level and rPSC development in LT recipients treated with fenofibrate

  36 months

• To quantify the associations between serum 7-alpha-hydroxy-4-cholesten-3-one level and rPSC development in LT recipients treated with fenofibrate

  36 months

Study Arms (2)

Treatment

EXPERIMENTAL

Individuals who underwent liver transplantation for primary sclerosing cholangitis 1-7 years before study initiation, and meeting study criteria, will receive fenofibrate 160mg oral daily for 36 months Participants will undergo the following serum assessments as part of the study every 3 months during the study period: total bile acids, bile acid profile, fibroblast growth factor 19, and 7-alpha-C4 Participants will undergo gadoxate-enhanced magnetic resonance imaging at baseline, 12 months, and 36 months.

Drug: Fenofibrate (drug); Diagnostic Test: Blood draw for the laboratory assessment; Diagnostic Test: MRI using a hepatobiliary phase contrast agent (Gd-EOB-DPTA)

Historical control

NO INTERVENTION

Historical control of individuals who underwent liver transplantation for primary sclerosing cholangitis who were not treated with any peroxisome proliferator activated receptor agonist treatment.

Interventions

Fenofibrate (drug) DRUG

Once daily fenofibrate for 36 months

Treatment

Blood draw for the laboratory assessment DIAGNOSTIC_TEST

Serum assessments will be performed every 3 months during the study period

Treatment

MRI using a hepatobiliary phase contrast agent (Gd-EOB-DPTA) DIAGNOSTIC_TEST

Participants will undergo a quantitative gadoxetate-enhanced MRI and MRCP at baseline, and at 12 months and 36 months of trial participation.

Treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18-75 irrespective of gender who have undergone LT for PSC or PSC-related liver malignancy between 1 year and 7 years (inclusive) prior to study enrollment
• Absence of rPSC at time of study enrollment
• At least one of the following additional features that increase risk of rPSC
• LT performed for cholangiocarcinoma
• Concurrent inflammatory bowel disease
• Any episode of cytomegalovirus viremia in the post-transplant period before study enrollment
• Any episode of acute cellular rejection in the post-transplant period before the study enrollment

You may not qualify if:

• Due to lab requirements, we will only enrol patients who are within a 3 hour driving distance of Mayo Clinic Arizona and/or are willing to travel to Mayo Clinic Arizona at 4 month intervals during the study at own cost.
• Presence of ischemic cholangiopathy which can mimic rPSC
• LT performed for primary biliary cholangitis or autoimmune hepatitis, or PSC with overlapping primary biliary cholangitis or autoimmune hepatitis, which may recur after LT and confound assessment of cholestasis
• Unaddressed post-LT hepatic artery compromise (e.g thrombosis, stenosis) which can mimic rPSC
• History of total colectomy for curative treatment of ulcerative colitis which reduces risk of rPSC
• Baseline GFR \<30 ml/min which precludes administration of fenofibrate
• Previously known intolerance or allergy to fenofibrate
• Other clinically significant comorbid condition, including inability to provide consent and psychiatric conditions, which in the opinion of the study team, may interfere with patient treatment, safety, assessment, or compliance with the treatment
• Female participants that are pregnant or planning to become pregnant

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Cholangitis, Sclerosing

Interventions

Fenofibrate; Pharmaceutical Preparations; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Phenyl Ethers; Ethers; Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols; Ketones; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Channa Jayasekera

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 28, 2025
• First Posted: April 1, 2025
• Study Start: April 15, 2025
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)