Fenofibrate for Primary Sclerosing Cholangitis

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Disqualifiers: Ischemic cholangiopathy, Primary biliary cholangitis, Autoimmune hepatitis, GFR <30 ml/min, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 36 months

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether fenofibrate, taken once daily for 36 months, can prevent the recurrence of primary sclerosing cholangitis (a liver disease) after a liver transplant. The researchers aim to compare results with past patients who did not receive this treatment. Individuals who underwent a liver transplant for this condition 1 to 7 years ago and have risks such as a history of certain liver issues or bowel disease may be suitable candidates. Participants must be able to travel to the Mayo Clinic in Arizona every four months. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team to understand any specific requirements.

Is there any evidence suggesting that fenofibrate is likely to be safe for humans?

Research has shown that fenofibrate is generally well-tolerated. In one study, 66.7% of patients with primary sclerosing cholangitis (PSC) responded well to fenofibrate, compared to only 20% who took a placebo. Another study found that fenofibrate lowered levels of alkaline phosphatase (ALP), a marker of liver health, in PSC patients. Although these studies don't list specific side effects, fenofibrate is already approved for other conditions, indicating a known safety profile. This ongoing trial will further evaluate its safety for PSC patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for primary sclerosing cholangitis?

Unlike the standard of care for primary sclerosing cholangitis, which often involves managing symptoms and complications with bile acid therapy or liver transplantation, fenofibrate offers a different approach. Fenofibrate is unique because it activates peroxisome proliferator-activated receptors (PPARs), which play a crucial role in regulating bile acid metabolism and inflammation. Researchers are excited about fenofibrate because it could potentially modify the disease process itself, rather than just alleviating symptoms, by targeting these metabolic pathways. This could lead to improved outcomes and a better quality of life for patients.

What evidence suggests that fenofibrate might be an effective treatment for primary sclerosing cholangitis?

Research has shown that fenofibrate, which participants in this trial will receive, might help treat primary sclerosing cholangitis (PSC). In one study, 66.7% of patients taking fenofibrate achieved the main treatment goal, compared to only 20% of those taking a placebo, indicating a significant improvement with fenofibrate. Other studies have also found that it helped lower alkaline phosphatase (ALP) levels, which are often high in people with PSC. While more research is needed, these findings suggest that fenofibrate could be useful in managing PSC. ^{1 2 3 6 7}

Who Is on the Research Team?

Channa Jayasekera

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for individuals who have had a liver transplant due to primary sclerosing cholangitis (PSC) and are at risk of recurrence. Specific eligibility criteria were not provided, but typically participants would need to meet certain health standards and may be required to have no history of allergic reactions to the interventions being tested.

Inclusion Criteria

I had a liver transplant for cancer, have bowel disease, or had certain infections or rejections after my transplant.

I had a liver transplant for PSC or related cancer between 1 and 7 years ago.

I can travel to Mayo Clinic Arizona every 4 months at my own expense.

Exclusion Criteria

I am pregnant or planning to become pregnant.

I have a condition that looks like rPSC affecting my bile ducts.

I had a liver transplant due to specific liver conditions and have unresolved issues with the liver's blood supply.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fenofibrate 160mg oral daily for 36 months to prevent clinically detectable rPSC after liver transplantation

36 months

Serum assessments every 3 months, MRI at baseline, 12 months, and 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Fenofibrate

Trial Overview The study tests if taking fenofibrate daily for 36 months can prevent PSC from coming back after a liver transplant. It's compared with past data where patients didn't get this treatment. Participants will also undergo MRI scans using Gd-EOB-DPTA contrast agent and regular blood tests.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 3 Interventions

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.

Group II: Historical control Active Control 1 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.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

In a study of 106 patients with primary biliary cholangitis (PBC) who did not respond well to ursodeoxycholic acid (UDCA), adding fenofibrate (FF) to their treatment significantly reduced alkaline phosphatase (ALP) levels and improved liver transplant-free survival after one year.

Patients receiving FF alongside UDCA showed better stabilization or improvement in liver fibrosis and bile duct loss compared to those on UDCA alone, indicating that FF may enhance the overall management of PBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fenofibrate improves GLOBE and UK-PBC scores and histological features in primary biliary cholangitis. Wang, L., Sun, K., Tian, A., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9277608/

Fenofibrate in primary sclerosing cholangitis; a randomized ... The primary endpoint was achieved in 66.7% of patients (10 in 15) in the fenofibrate group versus 20% of patients (3 in 15) in the placebo group (p = 0.009).

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1590865825000350

Fibrates in Primary Sclerosing Cholangitis: a multicenter ... In PSC patients, fibrates demonstrated significant ALP reduction, with 23.6% achieving normalization in 6 months. LSM remained stable at 12months.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35822553/

Fenofibrate in primary sclerosing cholangitis; a randomized ... The primary endpoint was achieved in 66.7% of patients (10 in 15) in the fenofibrate group versus 20% of patients (3 in 15) in the placebo group (p = 0.009).

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01142323

NCT01142323 | Pilot Study of Fenofibrate for PSC The purpose of this study is to determine whether fenofibrate is safe and effective in the treatment primary sclerosing cholangitis (PSC). Official Title.

5. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/abs/10.1002/prp2.984

Fenofibrate in primary sclerosing cholangitis; a randomized ... The primary endpoint was achieved in 66.7% of patients (10 in 15) in the fenofibrate group versus 20% of patients (3 in 15) in the placebo group ...

6. cghjournal.org cghjournal.org/article/S1542-3565(23)00277-X/fulltext

Recent Advances in the Management of Primary ... A recent, small, randomized, double-blind, placebo-controlled trial of patients with PSC showed a reduction in ALP level by 66% with fenofibrate ...

7. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.948362/full

Efficacy and safety of fenofibrate add-on therapy in patients ... Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incomplete UDCA response may improve outcomes.