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

NCT04550481 | Active Not Recruiting Phase 2 DMC FDA Drug

• 5 other identifiers: NCI-2020-06905NCI20-01-03NWU20-01-03P30CA060553UG1CA242643
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Hepatocellular Carcinoma; Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Change in PRO-C3 values

  Descriptive statistics will be used to summarize changes and values at each time point. The primary analysis will be performed using a paired t-test to compare the pre- to post-treatment changes in PRO-C3 levels. PRO-C3 levels will be log-transformed to satisfy the normality assumption. If log-transformation does not satisfy the normality assumption, a signed rank test will be used.

  Baseline to 24 weeks

Secondary Outcomes (7)

• Change in PC3X (cross-linked multimeric PRO-C3)

  Baseline to 24 weeks

• Change in steatosis

  Baseline to 24 weeks

• Change liver stiffness

  Baseline to 24 weeks

• Change liver stiffness

  Baseline to 24 weeks

• Change in non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS)

  Baseline to 24 weeks

Other Outcomes (6)

• Change in steatosis

  Baseline to 24 weeks

• Change in markers of liver injury and function: alanine aminotransferase, aspartate aminotransferase, bilirubin, and alkaline phosphatase

  Baseline to 24 weeks

• Change in homeostatic assessment of glycosylated hemoglobin

  Baseline to 24 weeks

Study Arms (1)

Prevention (lisinopril)

EXPERIMENTAL

Patients receive lisinopril PO QD for 24 weeks in absence of unacceptable toxicity. Patients undergo transient elastography during screening and on study. Patients also undergo blood sample collection on study and may undergo a PDFF MRI and MRE on study.

Procedure: Biospecimen Collection; Drug: Lisinopril; Procedure: Liver Ultrasonographic Elastography; Procedure: Magnetic Resonance Elastography; Procedure: Magnetic Resonance Imaging; Procedure: Proton Density Fat Fraction; Other: Questionnaire Administration

Interventions

Magnetic Resonance Elastography PROCEDURE

Undergo PDFF MRE

Also known as: MRE

Prevention (lisinopril)

Magnetic Resonance Imaging PROCEDURE

Undergo PDFF MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Prevention (lisinopril)

Proton Density Fat Fraction PROCEDURE

Undergo PDFF MRI/MRE

Also known as: Fat Fraction by Proton Density, PDFF

Prevention (lisinopril)

Questionnaire Administration OTHER

Ancillary studies

Prevention (lisinopril)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Prevention (lisinopril)

Lisinopril DRUG

Given PO

Also known as: N2-[(1S)-1-Carboxy-3-phenylpropyl]-L-lysyl-L-proline, Dihydrate, Prinivil, Zestril

Prevention (lisinopril)

Liver Ultrasonographic Elastography PROCEDURE

Undergo transient elastography

Also known as: Fibroscan, TE, Transient Elastography, VCTE, Vibration-Controlled Transient Elastrography

Prevention (lisinopril)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects \>= 18 years of age
• 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 up to six months prior to enrollment without suspicious nodules or cancer
• Screening transient elastography liver stiffness \>= 12 kPa (which correlates with F3 fibrosis and more) and \< 25 kPa. Historic transient elastography within 0-4 weeks prior to the date of the screening visit is acceptable. Patients with liver stiffness \>= 10 and \< 12 kPA with clinical evidence of cirrhosis based on any of the following criteria would also be eligible.
• Imaging diagnosis of nodular liver with splenomegaly or recanalized umbilical vein
• MRE \>= 5 kPa
• Fibrosis (FIB)-4 \> 2.67 or platelet count \< 150,000 mL
• Liver biopsy \< 5 years with meta-analysis of histological data in viral hepatitis (METAVIR) stage 4 or Ishak stage 5-6
• Controlled attenuation parameter score or liver steatosis analysis (LiSA) of \>= 260 dB/m and any single component of metabolic syndrome (ATP3 criteria) or historic liver biopsy within 0 - 6 months prior to the date of the screening visit consistent with nonalcoholic steatohepatitis (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
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 8 x institutional upper limit of institutional limits
• Glomerular filtration rate \> 30 ml/min
• International normalized ratio (INR) =\< 1.3 unless the patient is on a therapeutic medication

You may not qualify if:

• Prior or current use of an angiotensin converting enzyme inhibitor (ACEi) or angiotensin II receptor antagonist (ARB) within 0-24 weeks prior to enrollment
• Glomerular filtration rate =\< 30 ml/min (for both male and female participants)
• History of decompensated liver disease, including ascites, hepatic encephalopathy, or high-risk variceal bleeding
• NOTE: Trace ascites documented by radiology is permitted
• 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
• History of liver transplantation
• History of hepatocellular carcinoma (HCC) diagnosis
• 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 or psychiatric illness/social situations that would limit compliance with study requirements

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Non-alcoholic Fatty Liver Disease

Interventions

Specimen Handling; Lisinopril; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Fatty Liver

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Ju Dong Yang

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2020
• First Posted: September 16, 2020
• Study Start: May 11, 2021
• Primary Completion: August 8, 2025
• Study Completion (Estimated): September 30, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (4)