Statins for Non-alcoholic Steatohepatitis (NASH)

(STAT NASH Trial)

Recruiting at 1 trial location

Overseen By Amy Olofson

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Anti-NASH, Antidiabetics, Immune modulators

Disqualifiers: Chronic liver disease, Cirrhosis, Diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether atorvastatin, a medication commonly used to lower cholesterol, is safe and effective in improving non-alcoholic steatohepatitis (NASH), a liver condition marked by fat buildup and inflammation. Participants will receive either atorvastatin or a placebo for 96 weeks. The study seeks individuals with NASH confirmed by a recent liver biopsy who are not currently taking statins and have a specific level of liver scarring, known as fibrosis stage 2 or higher. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial requires that you are not currently on statin therapy and that you do not start any new anti-NASH therapies or certain antidiabetic medications. If you are taking any immune modulatory agents, you may also need to stop those. It's best to discuss your current medications with the trial team to see if they are allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that atorvastatin is generally safe for use. Studies have found it can cause mild muscle aches and temporary increases in liver enzymes, but these side effects are usually not serious for most people. Additionally, animal studies have demonstrated that atorvastatin reduces liver fat and inflammation, suggesting benefits beyond just lowering cholesterol. Overall, atorvastatin is considered safe and well-tolerated for treating conditions like NASH. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for NASH?

Most treatments for Non-alcoholic Steatohepatitis (NASH) focus on lifestyle changes and managing related health issues like diabetes and high blood pressure. Unlike these standard approaches, atorvastatin is being explored for its potential to directly reduce liver inflammation and fibrosis, which are critical aspects of NASH. Researchers are excited about atorvastatin because it’s primarily known as a cholesterol-lowering drug, but it may also help improve liver health by reducing the buildup of fats in the liver and decreasing inflammation, offering a more targeted approach to treating NASH.

What evidence suggests that atorvastatin might be an effective treatment for NASH?

This trial will compare atorvastatin with a placebo to evaluate its effectiveness for non-alcoholic steatohepatitis (NASH). Studies have shown that atorvastatin, a medication commonly used to lower cholesterol, might also help with NASH. Research suggests that statins, like atorvastatin, can improve liver health by reducing liver fat, inflammation, and scarring. Specifically, some studies found that patients who took atorvastatin experienced better liver health, with less liver fat and improved liver function. Additionally, atorvastatin has been linked to reducing inflammation and stress in the liver, which are major issues in NASH. These findings suggest that atorvastatin could be a promising treatment for people with NASH. ^{1 2 4 5 6}

Who Is on the Research Team?

Manal Abdelmalek, MD, MPH

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Adults aged 18-70 with a certain stage of liver scarring (fibrosis) and confirmed NASH, not on statins or other specific treatments for NASH. Participants must have had a recent liver biopsy showing definite NASH. They should not be heavy drinkers, have other serious health conditions, or be pregnant/breastfeeding. Women who can bear children must agree to use effective contraception.

Inclusion Criteria

I agree to use contraception if there is a chance that I could become pregnant.

My liver fibrosis stage is 2 or higher.

Provision of written informed consent

Exclusion Criteria

Inadequate venous access

I have a liver condition, but it's not NASH or related to drugs, viruses, autoimmune issues, or genetic disorders.

AST or ALT > 250 U/L

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atorvastatin or placebo for 96 weeks to evaluate safety and efficacy in improving NASH features

96 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atorvastatin
• Placebo

Trial Overview The trial is testing the safety and effectiveness of atorvastatin (Lipitor®), a cholesterol-lowering drug, in improving the condition of patients with Non-alcoholic Steatohepatitis (NASH). Some participants will receive atorvastatin while others will get a placebo to compare outcomes.

How Is the Trial Designed?

Group I: Group 1: Atorvastatin Treatment Experimental Treatment 1 Intervention

Subjects who have a histology-proved NASH with fibrosis stage 2 or higher will receive atorvastatin for 96 weeks

Group II: Group 2: Placebo Placebo Group 1 Intervention

Subjects who have a histology-proved NASH with fibrosis stage 2 or higher will receive a placebo for 96 weeks

Atorvastatin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in United States as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia
• Prevention of cardiovascular disease

Approved in Canada as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia
• Prevention of cardiovascular disease

Approved in Japan as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in China as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in Switzerland as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

Statins, particularly atorvastatin, have shown promising results in improving liver health and reducing cardiovascular disease (CVD) risk in patients with non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), based on analyses of over 11,000 participants from randomized controlled trials.

Statin treatment not only improves liver enzyme levels and liver imaging results but also significantly reduces CVD morbidity and mortality, with statin-treated NAFLD/NASH patients experiencing a 50% reduction in CVD events compared to those with normal liver function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statins: An Under-Appreciated Asset for the Prevention and the Treatment of NAFLD or NASH and the Related Cardiovascular Risk. Athyros, VG., Boutari, C., Stavropoulos, K., et al.[2022]

In a study of 42 patients with nonalcoholic steatohepatitis treated with atorvastatin for 12 months, significant improvements were observed in liver injury markers and metabolic profiles, including decreased liver transaminases and triglycerides, and increased beneficial adiponectin levels.

Atorvastatin's effectiveness in improving disease activity is linked to its ability to lower tumor necrosis factor-α levels, suggesting a mechanism by which it alleviates inflammation associated with nonalcoholic steatohepatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin improves disease activity of nonalcoholic steatohepatitis partly through its tumour necrosis factor-α-lowering property. Hyogo, H., Yamagishi, S., Maeda, S., et al.[2022]

High levels of PCSK9 in the liver and bloodstream contribute to the development of non-alcoholic fatty liver disease (NAFLD) by promoting fat storage and insulin resistance.

PCSK9 inhibitors not only help lower cholesterol but also protect the liver from NAFLD, showing potential benefits for patients with both NAFLD and cardiovascular disease, independent of their effects on LDL cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of PCSK9 in the Pathogenesis of Non-alcoholic Fatty Liver Disease and the Effect of PCSK9 Inhibitors. Theocharidou, E., Papademetriou, M., Reklou, A., et al.[2021]

In a 12-month double-blind randomized placebo-controlled trial involving 16 patients with biopsy-proven NASH, simvastatin treatment led to a 26% reduction in low-density lipoprotein (LDL) levels, indicating some lipid-lowering efficacy.

However, there was no significant improvement in liver function tests, liver fat content, inflammation, or fibrosis stage, suggesting that simvastatin monotherapy is not effective for treating NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study using simvastatin in the treatment of nonalcoholic steatohepatitis: A randomized placebo-controlled trial. Nelson, A., Torres, DM., Morgan, AE., et al.[2022]

Statins, particularly atorvastatin and rosuvastatin, have been shown to effectively reduce liver fat, inflammation, and fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), based on various observational and small clinical studies.

While ezetimibe has shown some efficacy in reducing liver fat, it lacks significant anti-inflammatory and anti-fibrotic effects, and other treatments like fibrates and omega-3 fatty acids have mixed results, indicating the need for further research to confirm their benefits in managing NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a role of lipid-lowering therapies in the management of fatty liver disease? Tzanaki, I., Agouridis, AP., Kostapanos, MS.[2022]

Lipid-lowering agents, such as statins and fibrates, have been found to be both safe and effective in treating patients with non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), potentially reducing liver fat accumulation.

Despite concerns about liver enzyme elevation (transaminitis) in patients treated with statins, the review of studies indicates that these treatments can be beneficial, highlighting the need for larger, well-designed randomized controlled trials to confirm their efficacy and safety in various patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid-lowering agents in nonalcoholic fatty liver disease and steatohepatitis: human studies. Nseir, W., Mograbi, J., Ghali, M.[2021]

Statins may help resolve nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), potentially improving cardiovascular disease (CVD) outcomes in affected patients, who are at higher risk of dying from CVD than liver disease.

Current evidence indicates that statins could significantly enhance symptom-free survival from CVD in patients with NAFLD/NASH, but further large randomized clinical trials are necessary to confirm these benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statins and nonalcoholic fatty liver disease: a bright future? Athyros, VG., Katsiki, N., Karagiannis, A., et al.[2014]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10828082/

Atorvastatin on Treatment of Nonalcoholic Fatty Liver ... The results indicate that statin use is associated with a lower prevalence of NASH and fibrosis and may have a preventive effect on NAFLD.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0753332224016925

Statins and non-alcoholic fatty liver disease: A concise review Statins show beneficial effects beyond lipid lowering by improving fibrosis, inflammation, oxidative stress and microcirculation in NAFLD/NASH.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19013295/

Efficacy of atorvastatin for the treatment of nonalcoholic ... Liver steatosis and nonalcoholic fatty liver disease activity score were significantly improved, whereas 4 patients had increased fibrosis stage. The NASH- ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04679376?term=AREA%5BBasicSearch%5D(nash)&rank=5

NCT04679376 | Statins for the Treatment of NASH The purpose of this research study is to determine whether the study drug, atorvastatin (Lipitor®), is safe and effective in improving the features of NASH .

5. mdpi.com mdpi.com/1420-3049/29/8/1859

A Systematic Review of Statins for the Treatment ... A study showed that atorvastatin reduced hepatic steatosis and inflammation induced by a high-saturated fat, high-fructose, and high-cholesterol diet in animals ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8652077/

Statins in Non-alcoholic Steatohepatitis - PMC Although all statins seem to be effective to reduce cholesterol in patients with NASH, atorvastatin has a favorable profile to reduce the ...