Role of Lisinopril in Preventing The Progression of Non-Alcoholic Fatty Liver Disease (NAFLD): Relief-NAFLD
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 35
- 试验地点
- 4
- 主要终点
- Change in PRO-C3 Values
研究概览
简要总结
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.
详细描述
PRIMARY OBJECTIVE:
I. To determine if NAFLD patients with advanced fibrosis will demonstrate a change in PRO-C3, a marker of liver fibrosis, following 24 weeks of treatment with lisinopril.
SECONDARY OBJECTIVES:
I. Noninvasive measures of fibrosis and steatosis:
Ia. Change from baseline in PC3X (cross-linked multimeric PRO-C3);
研究设计
- 研究类型
- 干预性
- 分配方式
- 不适用
- 干预模型
- 单组
- 主要目的
- 预防
- 盲法
- 开放（无盲法）
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 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
- 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
排除标准
- 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
- 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 >= 161 mm/Hg. Diastolic blood pressure >= 111 mm/Hg
- Participants taking lithium
研究组 & 干预措施
Prevention (lisinopril)
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.
干预措施: Magnetic Resonance Elastography (Procedure)
Prevention (lisinopril)
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.
干预措施: Biospecimen Collection (Procedure)
Prevention (lisinopril)
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.
干预措施: Liver Ultrasonographic Elastography (Procedure)
Prevention (lisinopril)
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.
干预措施: Magnetic Resonance Imaging (Procedure)
Prevention (lisinopril)
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.
干预措施: Proton Density Fat Fraction (Procedure)
Prevention (lisinopril)
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.
干预措施: Questionnaire Administration (Other)
Prevention (lisinopril)
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.
干预措施: Lisinopril (Drug)
方案终点
主要结局
Change in PRO-C3 Values
时间窗: Baseline to 24 weeks
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.
次要结局
- Change in PRO-C6 Value.(Baseline to 24 weeks)
- Change in Steatosis, Controlled Attenuation Parameter (CAP)(Baseline to 24 weeks)
- Change Liver Stiffness, Magnetic Resonance Elastography.(Baseline to 24 weeks)
- Change Liver Stiffness, Transient Elastography(Baseline to 24 weeks)
- Change in Non-alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS)(Baseline to 24 weeks)
- Change in Fibrosis-4 Score(Baseline to 24 weeks)
- Change in Inflammatory Markers (TGF-beta, TNF-alpha, IL-6 and IL-8)(Baseline to 24 weeks)
试验结果
结果已于 2026-08-14 在 ClinicalTrials.gov 公示。 在 ClinicalTrials.gov 查看
受试者流程
入组 35 人 · 完成 31 人
主要终点
Change in PRO-C3 Values
ng/mL · Standard Deviation · 时间窗: Baseline to 24 weeks
| 分类 | Prevention (Lisinopril) （n=31） |
|---|---|
| Pre-Treatment | 48 (17) |
| Post-Treatment | 49 (21) |
| Change | 1 (15) |
Participants with pre- and post-treatment samples.
其他终点（9）
Change in PRO-C6 Value.
ng/mL · Standard Deviation · 时间窗: Baseline to 24 weeks
| 分类 | Prevention (Lisinopril) （n=31） |
|---|---|
| Pre-treatment | 14.1 (5.6) |
| Post-treatment | 13.6 (4.3) |
| Change | -0.5 (5.1) |
Participants with pre- and post-treatment samples.
Change in Steatosis, Controlled Attenuation Parameter (CAP)
dB/m · Standard Deviation · 时间窗: Baseline to 24 weeks
| 分类 | Prevention (Lisinopril) （n=35） |
|---|---|
| Pre-treatment | 320 (39) |
| Post-treatment | 307 (63) |
| Change | -17 (43) |
Participants with pre- and/or post-treatment transient elastography.
Change Liver Stiffness, Magnetic Resonance Elastography.
Kilopascals (kPa) · Standard Deviation · 时间窗: Baseline to 24 weeks
| 分类 | Prevention (Lisinopril) （n=17） |
|---|---|
| Pre-treatment | 4.78 (1.88) |
| Post-treatment | 4.48 (2.01) |
| Change | -0.63 (0.88) |
Participants with magnetic resonance elastography pre- and/or post-treatment.
Change Liver Stiffness, Transient Elastography
Kilopascals (kPa) · Standard Deviation · 时间窗: Baseline to 24 weeks
| 分类 | Prevention (Lisinopril) （n=35） |
|---|---|
| Pre-treatment | 16.1 (3.5) |
| Post-treatment | 16.7 (8.9) |
| Change | 0 (8) |
Participants with transient elastography pre- and post-treatment.
Change in Non-alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS)
score on a scale · Standard Deviation · 时间窗: Baseline to 24 weeks
| 分类 | Prevention (Lisinopril) （n=35） |
|---|---|
| Pre-treatment | 0.02 (1.24) |
| Post-treatment | -0.01 (1.23) |
| Change | 0.02 (0.61) |
Participants with NAFLD fibrosis score (NFS).
Change in Fibrosis-4 Score
score on a scale · Standard Deviation · 时间窗: Baseline to 24 weeks
| 分类 | Prevention (Lisinopril) （n=35） |
|---|---|
| Pre-treatment | 2.10 (1.16) |
| Post-treatment | 2.17 (1.36) |
| Change | 0.12 (0.56) |
Participants with pre- and post-treatment Fibrosis-4 score.
Change in Inflammatory Markers (TGF-beta, TNF-alpha, IL-6 and IL-8)
pg/mL · Standard Deviation · 时间窗: Baseline to 24 weeks
| 分类 | Prevention (Lisinopril) （n=31） |
|---|---|
| TGF-beta Pre-treatment | 662 (244) |
| TGF-beta Post-treatment | 663 (244) |
| TGF-beta Change | 2 (190) |
| TNF-alpha Pre-treatment | 1.79 (0.68) |
| TNF-alpha Post-treatment | 1.84 (0.69) |
| TNF-alpha Change | 0.05 (0.57) |
| IL-6 Pre-treatment | 42 (48) |
| IL-6 Post-treatment | 45 (51) |
| IL-6 Change | 3 (26) |
| IL-8 Pre-treatment | 13 (9) |
| IL-8 Post-treatment | 16 (17) |
| IL-8 Change | 3 (16) |
Participants with pre- and post-treatment samples.
Change in Steatosis Measured by Magnetic Resonance Imaging-proton Density Fat Fraction.
percentage of fat · Standard Deviation · 时间窗: Baseline to 24 weeks
| 分类 | Prevention (Lisinopril) （n=18） |
|---|---|
| Pre-treatment | 9 (7) |
| Post-treatment | 8 (7) |
| Change | -0.38 (2.27) |
Participants with pre- and/or post-treatment magnetic resonance imaging-proton density fat fraction.
Change in Prognostic Liver Secretome Signature (PLSec) Score
score on a scale · Standard Deviation · 时间窗: Baseline to to 24 weeks
| 分类 | Prevention (Lisinopril) （n=31） |
|---|---|
| Pre-treatment | 3.26 (1.37) |
| Post-treatment | 2.81 (1.45) |
| Change | -0.45 (1.46) |
Participants with pre- and post-treatment samples.
安全性
| 组别 | 严重不良事件 | 死亡 |
|---|---|---|
| Prevention (Lisinopril) | 3 / 35 | 0 / 35 |
最常见的严重不良事件（人数）
| 事件 | Prevention (Lisinopril) |
|---|---|
| Catheter related infection | 1 / 35 |
| Hematemesis | 1 / 35 |
| Pancreatitis | 1 / 35 |
数值为申办方在 ClinicalTrials.gov 公示的原始数据，未经重新计算；括号内为公示的离散度（如 95% 置信区间）。
研究者
研究点 (4)
标识符
- NCT 编号
- NCT04550481
- 其他研究编号
- NCI-2020-06905, NCI-2020-06905, NCI20-01-03, NWU20-01-03, P30CA060553, UG1CA242643
日期
- 首次提交
- (6年前)
- 首次发布
- (6年前)
- 主要完成日期
- (去年)
- 研究完成日期
- (11小时前)
- 最近核实
- (9个月前)
- 最近更新
- (上个月)
监管与共享
- FDA 监管药物
- 是
- FDA 监管器械
- 否
- 个体参与者数据共享计划
- 是
- 是否有结果
- 是
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