What is the mechanism of action of this treatment?

Statins, such as simvastatin, inhibit the enzyme HMG-CoA reductase, essential for cholesterol synthesis in the liver. This inhibition lowers cholesterol levels and provides anti-inflammatory and antifibrotic effects, which are beneficial in managing liver cirrhosis. Additionally, statins may reduce the risk of hepatocellular carcinoma by blocking enzymes needed for cell growth. These mechanisms are crucial for liver cirrhosis patients as they offer potential benefits beyond cholesterol management, including protection against disease progression and liver cancer.

What side effects are associated with this type of intervention?

Simvastatin, a statin used to manage cholesterol levels, is being studied for its potential to prevent liver cancer in patients with liver cirrhosis. Common side effects of statins include muscle pain, liver enzyme abnormalities, and, in rare cases, rhabdomyolysis, a serious condition involving muscle breakdown. Other treatments for liver cirrhosis, such as ursodeoxycholic acid (UDCA) and obeticholic acid, can cause gastrointestinal symptoms, itching, and liver enzyme changes. Direct-acting antivirals (DAAs) for hepatitis C, a common cause of cirrhosis, are generally well-tolerated but can cause fatigue, headache, and nausea.

What prior FDA approvals exist?

The FDA has approved several treatments for liver cirrhosis, particularly focusing on managing complications and underlying causes. For instance, statins like Simvastatin, which block enzymes needed for cell growth, are being studied for their potential to prevent liver cancer in cirrhotic patients. Other treatments include antiviral medications for hepatitis-related cirrhosis and drugs like ursodeoxycholic acid for primary biliary cholangitis. Additionally, thrombopoietin receptor agonists such as eltrombopag and avatrombopag have been used to manage thrombocytopenia in cirrhotic patients.

What other types of research exist?

Promising novel alternatives to Simvastatin for liver cirrhosis patients include PCSK9 inhibitors like Evolocumab, which have shown long-term efficacy and safety in lowering LDL-C levels. Additionally, monoclonal antibodies to ANGPTL3, such as Evinacumab, are under investigation and have demonstrated significant LDL-C reduction in clinical trials. These alternatives may offer new therapeutic options for managing liver cirrhosis and associated dyslipidemia.

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HMG-CoA Reductase Inhibitor

Simvastatin for Preventing Liver Cancer in Patients With Cirrhosis

Phase 2

Waitlist Available

Led By Marc T Goodman

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to 6 months

Summary

This trial studies if simvastatin can prevent liver cancer in patients with liver cirrhosis. Simvastatin, usually used to lower cholesterol, might block enzymes that cancer cells need to grow. The trial targets patients with liver disease. Simvastatin has been shown to reduce the risk of liver cancer and improve outcomes in these patients.

Who is the study for?

Adults with liver cirrhosis who are not pregnant or breastfeeding, have not had a liver transplant or certain cancers, and do not drink excessively can join. They must be in fairly good health otherwise, with specific blood test results within acceptable ranges and able to use birth control if necessary.

What is being tested?

The trial is testing whether simvastatin can prevent liver cancer in patients with liver cirrhosis. Participants will either receive simvastatin or a placebo while undergoing regular monitoring through imaging tests like CT scans and MRIs, as well as providing biospecimens.

What are the potential side effects?

Simvastatin may cause muscle pain, digestive issues, increased blood sugar levels, and memory problems or confusion. It's also important for women to know that it could harm an unborn baby if they become pregnant during the trial.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to 6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to 6 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in serum AFP-L3%

Secondary study objectives

Change in Model for End-Stage Liver Disease score

Change in fibrosis 4 index score

Liver

+3 more

Other study objectives

Change in serum bile acids

Change in serum immune markers

Side effects data

From 2015 Phase 3 trial • 33 Patients • NCT02030041

11%

Myalgia

100%

80%

60%

40%

20%

Study treatment Arm

Vitamin D and Placebo

Simvastatin and Placebo

Simvastatin and Vitamin D

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Group I (simvastatin)Experimental Treatment5 Interventions

Patients receive simvastatin PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood on study and CT/MRI throughout the trial.

Group II: Group II (placebo)Placebo Group5 Interventions

Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood on study and CT/MRI throughout the trial.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biospecimen Collection

2004

Completed Phase 3

~2030

Computed Tomography

2017

Completed Phase 2

~2790

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

Simvastatin

2012

Completed Phase 4

~1270

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Statins, such as simvastatin, inhibit the enzyme HMG-CoA reductase, essential for cholesterol synthesis in the liver. This inhibition lowers cholesterol levels and provides anti-inflammatory and antifibrotic effects, which are beneficial in managing liver cirrhosis. Additionally, statins may reduce the risk of hepatocellular carcinoma by blocking enzymes needed for cell growth. These mechanisms are crucial for liver cirrhosis patients as they offer potential benefits beyond cholesterol management, including protection against disease progression and liver cancer.

Pharmacotherapies that specifically target ammonia for the prevention and treatment of hepatic encephalopathy in adults with cirrhosis.Assessment and Management of Sleep Disturbance in Cirrhosis.Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.