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?

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.

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 atorvastatin safe for humans, especially for those with liver conditions like NASH?

Research suggests that atorvastatin is generally safe for humans, including those with liver conditions like NASH. Studies show it can improve liver health and reduce heart disease risk without significant safety concerns. ^{1 2 3 4 5}

How does the drug Atorvastatin differ from other treatments for NASH?

Atorvastatin is unique for NASH treatment because it not only helps improve liver health by reducing liver enzymes and inflammation but also significantly lowers the risk of cardiovascular disease, which is a major concern for NASH patients. Unlike other treatments, it has shown promising results in both liver and heart health without the common side effects associated with other drugs like pioglitazone. ^{2 3 5 6 7}

What evidence supports the effectiveness of the drug atorvastatin for treating non-alcoholic steatohepatitis (NASH)?

Research shows that atorvastatin can improve liver health in NASH patients by reducing liver enzymes and improving liver imaging results. It also significantly lowers the risk of heart-related problems in these patients. ^{2 3 5 6 7}

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 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]

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]

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. United Arab Emirates 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A pilot study using simvastatin in the treatment of nonalcoholic steatohepatitis: A randomized placebo-controlled trial. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Atorvastatin improves disease activity of nonalcoholic steatohepatitis partly through its tumour necrosis factor-α-lowering property. [2022]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The Role of PCSK9 in the Pathogenesis of Non-alcoholic Fatty Liver Disease and the Effect of PCSK9 Inhibitors. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Is there a role of lipid-lowering therapies in the management of fatty liver disease? [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Lipid-lowering agents in nonalcoholic fatty liver disease and steatohepatitis: human studies. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Statins and nonalcoholic fatty liver disease: a bright future? [2014]