A Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Efficacy and Safety of Misocholic Film-Coated Tablets in Patients With Non-Viral Elevated Liver Enzymes
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in serum ALT and AST levels from baseline to Day 30
研究概览
简要总结
Elevated liver enzymes are common laboratory abnormalities that may result from alcohol-related liver disease, drug-induced liver injury, or non-alcoholic fatty liver disease (NAFLD). Persistent elevation of liver enzymes may indicate ongoing hepatocellular injury and increase the risk of progressive liver disease. Current management primarily focuses on treating the underlying cause and providing supportive care, while evidence for effective hepatoprotective therapies remains limited.
This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the efficacy and safety of Misocholic Tab, a film-coated herbal medicine, in adults with mild to moderate elevation of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) associated with alcohol-related liver disease, drug-induced liver injury, or non-alcoholic fatty liver disease. Eligible participants will be randomly assigned in a 1:1 ratio to receive either Misocholic Tab or matching placebo for 30 days. Both groups will receive standard background therapy with silymarin.
The primary objective is to compare the change in serum ALT and AST levels from baseline to Day 30 between the two treatment groups. Secondary objectives include evaluating the proportion of participants whose liver enzyme levels return to the normal range and assessing the safety of Misocholic Tab through clinical evaluation, laboratory testing, and monitoring of adverse events.
详细描述
Elevated liver enzymes are among the most common abnormalities encountered in clinical practice and often reflect hepatocellular injury. Alcohol-related liver disease (ALD), drug-induced liver injury (DILI), and non-alcoholic fatty liver disease (NAFLD) are major causes of elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Persistent elevation of liver enzymes may indicate ongoing liver injury and is associated with progression to fibrosis, cirrhosis, or liver failure if the underlying condition is not adequately controlled.
Current management primarily consists of eliminating or controlling the underlying cause, including alcohol abstinence, withdrawal of potentially hepatotoxic medications, lifestyle modification, and supportive treatment. Although several hepatoprotective agents are used in clinical practice, evidence supporting their efficacy remains limited, and additional randomized controlled trials are needed.
Misocholic Tab is a film-coated herbal medicine developed from a traditional formulation containing dried pig bile extract, artichoke extract, garlic powder, and activated charcoal. Preclinical studies have demonstrated favorable safety profiles as well as hepatoprotective, antioxidant, and anti-fibrotic effects in experimental models of alcohol-induced liver injury, drug-induced liver injury, and liver fibrosis. However, clinical evidence regarding its efficacy and safety in patients with elevated liver enzymes is currently limited.
This study is a prospective, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of Misocholic Tab in adult patients with mild to moderate elevation of ALT and/or AST associated with alcohol-related liver disease, drug-induced liver injury, or non-alcoholic fatty liver disease. Eligible participants will be randomly assigned in a 1:1 ratio to receive either Misocholic Tab or matching placebo for 30 days. Both groups will receive background therapy with silymarin according to the study protocol.
The primary efficacy endpoint is the change in serum ALT and AST levels from baseline to Day 30. Secondary endpoints include the absolute and percentage changes in liver enzyme levels, the proportion of participants achieving normalization of liver enzymes, and the assessment of safety through clinical evaluation, laboratory testing, and monitoring of adverse events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants, care providers, investigators, and outcome assessors will be blinded to treatment allocation. The treatment allocation code will be maintained by an independent pharmacist and will be unblinded only in the event of a medical emergency or other predefined circumstances.
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
- •Adults aged 18 years or older.
- •Mild to moderate elevation of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) at screening, defined as ALT and/or AST ≥2 to <5 times the upper limit of normal (ULN) according to the reference range of the study laboratory.
- •Elevated liver enzymes primarily associated with one of the following conditions:
- •Alcohol-related liver disease (ALD), defined by: History of hazardous alcohol consumption for at least the previous 3 months (average ethanol intake ≥40 g/day for men or ≥20 g/day for women); Elevated ALT and/or AST consistent with hepatocellular liver injury; At least one supportive feature of alcohol-related liver disease (e.g., elevated GGT, AST/ALT ratio ≥1, hepatomegaly, right upper quadrant discomfort, or hepatic steatosis on ultrasonography); No other liver disease considered the primary cause of liver enzyme elevation.
- •Drug-induced liver injury (DILI), defined by: Exposure to conventional medications, herbal medicines, traditional medicines, or dietary supplements within 180 days before detection of elevated liver enzymes; A reasonable temporal relationship between exposure and liver enzyme elevation; Hepatocellular or mixed liver injury pattern with predominant ALT/AST elevation; RUCAM score classified as possible or higher; No other liver disease considered the primary cause of liver enzyme elevation.
- •Non-alcoholic fatty liver disease (NAFLD), defined by: Evidence of hepatic steatosis on ultrasonography; Elevated ALT and/or AST consistent with hepatocellular liver injury; Alcohol consumption below the diagnostic threshold for alcohol-related liver disease; No other liver disease considered the primary cause of liver enzyme elevation. Willing to comply with study recommendations for management of the underlying cause, including alcohol abstinence or maximal reduction of alcohol intake when appropriate, discontinuation, substitution, or stabilization of suspected hepatotoxic medications or products when clinically feasible, and maintenance of stable background therapy throughout the study.
- •Willing to avoid the use of additional hepatoprotective drugs, herbal medicines, or dietary supplements that may significantly affect liver enzyme levels during the study unless medically required.
- •Able and willing to provide written informed consent.
排除标准
- •Evidence or reasonable suspicion of another liver disease that is considered the primary cause of elevated liver enzymes, including:
- •Positive hepatitis B surface antigen (HBsAg) or hepatitis C virus infection (anti-HCV or HCV RNA positive);
- •Suspected acute viral hepatitis (including hepatitis A or E when clinically indicated);
- •Biliary obstruction, gallstones, biliary tract dilation, hepatic or biliary malignancy, or pancreaticobiliary disease identified by imaging;
- •Autoimmune liver disease, Wilson disease, hemochromatosis, alpha-1 antitrypsin deficiency, or other chronic liver diseases other than NAFLD.
- •Severe liver injury or advanced liver disease, including:
- •ALT or AST ≥5 × ULN;
- •Total bilirubin ≥2 × ULN or clinically significant jaundice;
- •INR ≥1.5 (in participants not receiving anticoagulants);
- •Serum albumin <30 g/L;
- •Platelet count <100 × 10⁹/L;
- •Clinical, laboratory, or imaging evidence of advanced cirrhosis or portal hypertension;
- •Ascites, hepatic encephalopathy, gastrointestinal bleeding related to portal hypertension, or decompensated cirrhosis;
- •Requirement for urgent hospitalization or specialist treatment because of liver disease.
- •Predominantly cholestatic liver injury, including ALP ≥2 × ULN or liver injury pattern considered unsuitable for evaluation of hepatocellular enzyme reduction.
- •Extrahepatic causes of elevated aminotransferases, including rhabdomyolysis, acute muscle injury, excessive recent exercise, recent myocardial infarction, severe heart failure, congestive hepatopathy, shock, or severe systemic infection.
- •Use of hepatoprotective medications, herbal medicines, or dietary supplements that may influence liver enzymes within 4 weeks before screening.
- •Inability to discontinue alcohol consumption or stabilize suspected hepatotoxic medications or products during the study.
- •Pregnant or breastfeeding women, or women planning pregnancy during the study period.
- •Known hypersensitivity to any component of Misocholic Tab.
- •Uncontrolled severe medical illness, active malignancy, or any condition that, in the opinion of the investigator, would make participation inappropriate or unsafe.
- •Participation in another interventional clinical trial.
- •Inability or unwillingness to comply with study procedures, scheduled visits, study medication, or protocol-required assessments.
研究组 & 干预措施
Misocholic Tab
Participants will receive Misocholic Tab (1 tablet orally, three times daily after meals) for 30 days in addition to background therapy with silymarin.
干预措施: Misocholic Tab (Drug)
Misocholic Tab
Participants will receive Misocholic Tab (1 tablet orally, three times daily after meals) for 30 days in addition to background therapy with silymarin.
干预措施: Silymarin (Silybum marianum) (Drug)
Placebo
Participants will receive matching placebo (1 tablet orally, three times daily after meals) for 30 days in addition to background therapy with silymarin.
干预措施: Placebo (Drug)
Placebo
Participants will receive matching placebo (1 tablet orally, three times daily after meals) for 30 days in addition to background therapy with silymarin.
干预措施: Silymarin (Silybum marianum) (Drug)
结局指标
主要结局
Change in serum ALT and AST levels from baseline to Day 30
时间窗: Baseline and Day 30
Change in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations between baseline (Day 0) and the end of treatment (Day 30). The primary efficacy analysis will compare the mean change in ALT and AST levels between the Misocholic Tab group and the placebo group.
次要结局
- Percentage change in serum ALT and AST levels(Baseline and Day 30)
- Normalization of liver enzyme levels(Day 30)
- Safety and tolerability(Baseline to Day 30)