Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
Inclusion Criteria:
- 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 (Fibroscan) liver stiffness ≥ 12 kPa (which
correlates with F3 fibrosis and more) and < 25 kPa. Historic transient elastography
(Fibroscan) within 0-4 weeks prior to the date of the screening visit is acceptable.
- Controlled attenuation parameter score of ≥ 270 dB/m or historic liver biopsy within
0-6 months prior to 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.
- 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.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%).
- 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 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
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.
- 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.
- 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
econdary to treatment of the mother with lisinopril. Breastfeeding should be discontinued if
he mother is treated with lisinopril.
- Systolic blood pressure ≥ 161 mm/Hg. Diastolic blood pressure ≥ 111 mm/Hg.
- Participants taking lithium.