Role of Lisinopril in Preventing the Progression of Non-Alcoholic Fatty Liver Disease, RELIEF-NAFLD Study

ID#: NCT04550481

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 2

Recruitment Status: Recruiting

Start Date: April 01, 2021

End Date: March 31, 2023


This phase II trial investigates how well lisinopril may work in preventing the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD is a condition where there is an accumulation of fatty cells in the liver. NAFLD increases a person's risk of developing liver cancer. Liver fibrosis is the common finding of chronic liver diseases leading to reduced liver function. Lisinopril is a medication that is commonly used to treat high blood pressure. Lisinopril may help to decrease liver fibrosis. The purpose of this trial is to find out what effect, if any, lisinopril has on a patient's risk of developing liver cancer.


Inclusion Criteria:

- Clinical diagnosis of nonalcoholic steatohepatitis (NASH) assessed by the presence of body imaging criteria (ultrasound, computed tomography [CT], or magnetic resonance imaging [MRI]), or liver biopsy

- Screening transient elastography (Fibroscan) liver stiffness >= 12 kPa (which correlates with F3 fibrosis and more) and < 20 kPa. Historic transient elastography (Fibroscan) within 4 weeks of the date of the screening visit is acceptable

- Controlled attenuation parameter score of >= 270 dB/m or historic liver biopsy within 6 months of the date of the screening visit consistent with NASH (defined as the presence of steatosis, inflammation, and ballooning), with stage 3-4 fibrosis according to the NASH Clinical Research Network classification (or equivalent)

- Leukocytes >= 3,000/microliter

- Absolute neutrophil count >= 1,500/microliter

- Platelets >= 75,000/microliter

- Total bilirubin within normal institutional limits unless the patient has Gilbert's syndrome

- AST (serum glutamic oxaloacetic transaminase [SGOT])/ALT (serum glutamic pyruvic transaminase [SGPT]) =< 8 x institutional upper limit of institutional limits

- Glomerular filtration rate > 30 ml/min

- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

- The effects of lisinopril has been shown to be teratogenic in animal models. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately

- Ability to understand and the willingness to sign a written informed consent document. If a participant has impaired decision-making capacity (IDMC), their legal representative may replace them in this process

- Systolic blood pressure > 90 and < 160 mm/Hg. Diastolic blood pressure > 60 and < 110 mm/Hg

Exclusion Criteria:

- Prior or current use of an angiotensin converting enzyme inhibitor (ACEi) or angiotensin II receptor antagonist (ARB) within 24 weeks of enrollment

- Glomerular filtration rate =< 30 ml/min

- History of decompensated liver disease, including ascites, hepatic encephalopathy, or variceal bleeding

- History of other causes of liver disease, including but not limited to alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders (primary biliary cholangitis, primary sclerosing cholangitis, or autoimmune hepatitis), drug-induced hepatotoxicity, Wilson's disease, iron overload, or alpha-1-antitryspin deficiency

- Focal lesions on baseline magnetic resonance imaging (MRI) must be resolved

- History of liver transplantation

- History of hepatocellular carcinoma (HCC)

- History of weight reduction surgery in the past 2 years or planned during the study

- Within 6 months prior to the date of the screening visit, there must be no history of the following cardiac events: unstable angina; myocardial infarction, coronary artery bypass surgery or coronary angioplasty; transient ischemic attack or cerebrovascular accident; emergency room visit or hospitalization for confirmed cardiovascular disease

- Participants taking vitamin E >= 800 IU/day must be on a stable dose, defined as no changes in prescribed dose, new vitamin E-containing medications, or discontinuation for at least 180 days prior to the date of the screening visit and throughout study participation

- Participants taking anti-diabetic medications must be on a stable dose for at least 90 days prior to the date of the screening visit and in the period between the date of the screening visit and enrollment

- Current alcohol consumption > 21 oz/week for males or > 14 oz/week for females (1 oz/30 mL of alcohol is present in one 12 oz/360 mL beer, 4 oz/120 mL glass of wine, and a 1oz/30 mL measure of 40 proof [20%] alcohol)

- Participants may not be receiving any other investigational agents, at the time of the screening visit, or in the prior 30 days, or within 5 half-lives of the prior investigational agent (whichever is longer)

- History of allergic reactions attributed to compounds of similar chemical or biologic composition to lisinopril

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

- History of human immunodeficiency virus (HIV) infection. HIV patients may develop fatty liver as well as advanced fibrosis due to many causes including metabolic syndrome, hyperuricemia, HIV-related lipodystrophy, genetic polymorphisms, medications, and HIV itself. As the natural history of fatty liver in this population is largely unknown, these patients will be excluded from this study

- Women who are pregnant or breastfeeding. Pregnant women are excluded from this study because lisinopril is an ACE Inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with lisinopril. Breastfeeding should be discontinued if the mother is treated with lisinopril

- Systolic blood pressure > 160 mm/Hg. Diastolic blood pressure > 110 mm/Hg

- Participants taking lithium