What is the difference in the treatment efficacy of two different dose regimes of LLC against placebo in patients with metabolic (dysfunction)-associated fatty liver disease (MAFLD)?

Setting: The study will be conducted at the liver clinic of Colombo North Teaching Hospital, Ragama. The study will recruit consenting patients diagnosed with MAFLD who fulfill the specified inclusion and exclusion criteria of the trial. The patients that are excluded will receive standard care provided by the liver clinic of Colombo North Teaching Hospital, Ragama.

Enrollment: Advertisement about the details of the study and contact number of PI will display in three language (Sinhala/English/Tamil) at the Liver Clinic at Colombo North Teaching Hospital, Ragama. Interesting participants will contact PI and they will be approached by a trained medically qualified research assistant who has completed GCP training.

Randomization: Simple randomization method using computer-generated random numbers. The patients will be randomized in a 1:1:1 ratio.

Blinding: Neither participants, nor investigators, nor data collectors nor the study team nor data analysts will be aware of treatment assignments prior to the final breaking of codes of database. The codes of database will be opened after completion of the data analysis and conclusion of the study.

Intervention: The LLC and placebo tablets will be manufactured in identical shape and size and will be film coated to give the same appearance. Both LLC tablets and placebo tablets will be packed into identical white HDPE (High Density Polyethylene) plastic bottles numbered from 1 to 294 by a senior R&D Scientist (Pharmacist) at Link Natural Products (Pvt.) Ltd. according to the list of computer-generated random numbers. The label of each bottle will indicate only the patient’s random number and the directions for taking the tablets. Each bottle contains medication/ placebo required for 30 days. Dosage form of LLC and placebo is a tablet. Patients will be asked to take the medication as one tablet (Low dose group) or two tablets (High dose group) every day after the dinner. The duration of the study is 12 months. LLC tablet comprises of fourteen herbal ingredients namely Andrographis paniculata, Eclipta prostrata, Phyllanthus amarus, Phyllanthus emblica, Terminalia chebula, Terminalia bellerica, Tinospora cordifolia, Curcuma longa, Glycyrrhiza glabra, Boerhavia diffusa, Osbeckia octandra, Tephrosia purpurea, Piper longum and Cyanthillium cinereum.

The placebo tablet comprises, microcrystalline cellulose BP., maize starch BP., sodium starch glycolate BP., carboxymethyl cellulose BP., Aerosil 200 Pharma., and magnesium stearate BP [All excipients in the investigational medicine other than the active ingredient is included].

Participants must meet all the following inclusion criteria to be eligible for enrollment into the study: 1.Both male and non-pregnant, non-lactating female patients aged 18 - 75 years who provide written informed consent before starting the study. 2.Who had undergone FibroScan within the 3 months of period showing a liver-stiffness measurement of 10-15 kPa. 3.MAFLD patients diagnosed based on following criteria: Ultrasonically proven of hepatic steatosis in conjunction with at least one of following criteria. a. Overweight/ obesity (BMI 23 kg/m2 in Asians) or WC > 90 cm (male) 80 cm (Female) b. Prediabetes: HbA1c 39-47 mmol/mol (5.7-6.4%) or fasting plasma glucose 5.6-6.9 mmol/L (100-125 mg/dl) or 2-h plasma glucose during OGTT 7.8-11 mmol/L (140-199 mg/dl) or Type 2 diabetes: HbA1c 48 mmol/mol (6.5%) or fasting plasma glucose 7.0 mmol/L (126 mg/dl) or 2-h plasma glucose during OGTT 11.1 mmol/L (200 mg/dl) or Treatment for type 2 diabetes. c. Plasma triglycerides 1.7 mmol/L (150 mg/dl) or lipid-lowering treatment. d. HDL-cholesterol 1.0 mmol/L (39 mg/dl) in men and 1.3 mmol/L (50 mg/dl) in women or lipid-lowering treatment. e. Blood pressure 130/85 mmHg or treatment for hypertension. 4.Participants should have been on a stable dose of anti-diabetic medication and hypolipidemic drugs if they are taking any for at least 3 months prior to entry. 5.Participants who are not on any medical treatment or herbal supplements for NAFLD/MAFLD.

1.Those with a history of significant alcohol consumption. (more than 20 g/day for women and 30g/day for men ? 2 units alcohol/day for women and >3 units for men). 2.Volunteers with known other potential causes of liver disease other than NAFLD/MAFLD including Hepatitis B, Hepatitis C, Dengue hepatitis, chronic viral hepatitis, autoimmune and hereditary liver disease. 3.Continued use of drugs historically associated with NAFLD/MAFLD (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, and other known hepatotoxins) for more than 2 weeks in the 6 months prior to randomization. 4. Volunteers who have undergone recent surgery. 5. Volunteers on any medicines, including nutritional, Ayurveda/ herbal supplements. 6. Any women currently pregnant as excluded (by a positive hCG test)/ planning to get pregnant during the study period. 7. Allergies or allergic reactions to any of the ingredients of LLC. 8. Presence of definite or probable drug-induced liver injury. In the case of lipid lowering, anti-hypertensive or anti-diabetic medications that are suspected to cause elevation of aminotransferases, patients will be eligible if treatment is associated with stable enzyme levels for at least 6 months. 9. Chronic kidney disease. 10. Presence of clinical, radiological, biochemical and or endoscopic evidence of cirrhosis. 11. Any condition that, in the opinion of the clinician, would contraindicate the patient’s participation. 12. Patients who are on pharmacological treatment for MAFLD.