Efficacy and Safety of Picroliv in Patients With Non-Alcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease (NAFLD) is a highly prevalent metabolic liver disorder with limited pharmacological treatment options. Lifestyle modification remains the mainstay of management, highlighting the need for safe and effective therapeutic agents.

Picroliv®, a standardized ethanolic extract of the roots and rhizomes of Picrorhiza kurroa, has demonstrated hepatoprotective, antioxidant, and anti-inflammatory properties in preclinical studies and early clinical investigations.

This Phase III, multicentre, randomized, double-blind, placebo-controlled, two-arm interventional study is designed to evaluate the efficacy and safety of Picroliv in adults diagnosed with uncomplicated NAFLD (fibrosis stage up to F2). Eligible participants aged 18-60 years will be randomized in a 2:1 ratio to receive either Picroliv 100 mg capsules twice daily or matching placebo, in addition to standard of care, for 24 weeks.

Standard of care includes dietary counseling, exercise recommendations, and management of associated comorbidities as per routine clinical practice. Participants will be followed for a total study duration of 48 weeks. The study will be conducted at six clinical centers in India.

Inclusion criteria

• Age: 18- 60 years
• Sex: Both males and females
• Patients showing presence of hepatic fat fraction as defined by ≥ 10% on MRI-PDFF at screening.
• Liver enzymes normal or above the ULN (upper limit of normal range) but less than 3 times
• Hemoglobin ≥10 g/dL, a platelet count ≥ 100 x 109/L, and a white blood cell count ≥ 3.0 x 109/L
• HbA1c < 7% (if participant has Type 2 diabetes mellitus (T2DM) should be controlled with appropriate treatment for the same except thiazolidinediones)
• TSH within normal limits (WNL) at screening
• If on metformin, sulfonylureas, statins, or fibrates, subjects must be on a stable dose of these drugs for at least three months prior to Screening and during the study will be allowed if on stable doses in the preceding 12 weeks and will be continued throughout the study.

Exclusion criteria

• Significant alcohol consumption (> 210 g/week in males and > 70 g/week in females)
• eGFR < 60 mL/min / 1.73m2 or patients on dialysis
• Hepato-biliary disorders: Cirrhosis, biliary obstruction, chronic cholecystitis, cholelithiasis, active or chronic active Hepatitis B or hepatitis C, autoimmune liver diseases
• Medical conditions including stroke, Alzheimer's disease, tuberculosis, Ischemic Heart Disease (IHD), Deep Vein Thrombosis (DVT), pancreatitis, inflammatory rheumatic diseases, cancer or any disorder that may potentially impact the outcome measures
• Patients on drugs potentially associated with NAFLD such as amiodarone, methotrexate, perhexiline, estrogens, tamoxifen, nifedipine, diltiazem, chloroquine and other hepatotoxic agents as per the discretion of the study investigator.
• Medications for disease conditions (e.g., HIV-1, HBV, or HCV infection, active cancer, transplantation are also excluded from the study.
• Subjects on anti TNF therapies, other biologicals and probiotics
• Subjects on Thiazolidinediones (TZDs), Saroglitazar, Atazanavir, Indinavir, Ketoconazole, Valproic acid, Silybum marianum, Valeriana officinalis and hepatoprotective plants / Traditional medicine formulations / natural products.
• Subjects on medications that may affect glucose metabolism such as corticosteroids, opiates, barbiturates and anticoagulants.
• Any disorder or clinically significant finding that may potentially impact the outcome measures as per the discretion of the study investigator.
• Pregnant and lactating women.
• Patients with a history of serious drug allergies (such as anaphylactic shock)
• Not willing to provide written informed consent
• Females unwilling to use any form of contraception during the trial.