Clinical Trial to Investigate the Anti-oxidant Activity of Heptex in Patients With Apparent Risk Factors of NASH

This is a phase II, randomized, double blind placebo-controlled, three-arm, parallel-group, intervention clinical trial evaluating anti-oxidant activity of Heptex; a herbal medicinal product of Aerial Parts of Phyllanthus niruri (Dukung Anak) and Fruits of Silybum marianum (Milk Thistle) in patients with apparent risk factors of NASH.

Inclusion criteria

• Male or female aged between 18 and 65 years.
• Both male and female patients who have childbearing potential must agree to practice an acceptable method of birth control during the study and for at least 6 months after the cessation of treatment; such contraceptive methods must include at least one barrier method.
• Controlled Attenuation Parameter (CAP)-confirmed hepatic steatosis.
• Patients with elevated serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels but less than 2.5 times the upper limit of the normal range.
• Liver fibrosis stage F1-F2 as diagnosed by the FibroScan liver stiffness measurement of 5-10 kPa.
• Liver condition according the following criteria;

• Serum albumin > 3 g/dl
• INR < 2
• No ascites on ultrasound
• No documented or suspected hepatic encephalopathy
• Willing to stop any other liver support and hepatoprotective medications throughout study duration.
• Able and willing to provide written informed consent.
• Able and willing to complete all study visits and procedures, including compliance with the requirements and restrictions listed in the consentform.

Exclusion criteria

• Pregnant or lactating women.
• Patients with BMI > 40 Kg/m2 or BMI < 18.5 Kg/m2.
• Serum creatinine > 1.5 x ULN OR creatinine clearance (GFR) < 60 mL/minute.
• Platelet count < 75,000/mm3.
• Uncontrolled diabetes mellitus as evident by HbA1c ≥ 8.5%.
• Patients who are currently receiving Thiazolidinediones.
• Patients with ischemic heart disease (IHD).
• History of parenteral nutrition.
• History of liver transplant.
• Viral hepatitis, drug-induced liver injury, metabolic liver disease or auto-immune liver disease.
• Liver cancer or serum alpha-fetoprotein (AFP) >100ng/ml. Patients with an AFP between 50 and 100ng/ml may be included as long as a liver ultrasound within 3 months of screening, or at screening, shows no evidence of potential hepatocellular cancer.
• Use of drugs known to induce steatosis (valproate, amiodarone or prednisone) or to affect body weight and carbohydrate metabolism.
• Use of drugs known to alter liver enzymes.
• Allergy or allergic history to any of the drug components.
• History of alcohol abuse as assessed by the investigator within the past 2 years, or an alcohol use pattern that may interfere with the patient's study compliance. Patients must have abstained from alcohol for at least 6 months prior to study start.
• Patients with history of clinically-significant illness or any other major medical disorder that may interfere with subject treatment, assessment, or compliance with the protocol.
• Receipt of an investigational drug within 6 months prior to screening, or active enrolment in another investigational medication or device trial.
• Patients with any chronic illness or prior treatment which in the opinion of the investigator should preclude participation in the trial.
• Inability to understand and cooperate with the investigators or to give valid consent.