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

Official title

A Phase III, Multicentre, Randomized, Double-blind, Placebo-controlled, Interventional Study on Efficacy and Safety of Standardized Fraction of Picrorhiza Kurroa Royal Ex Benth (Picroliv®) for 24 Weeks in the Management of Non-Alcoholic Fatty Liver Disease (NAFLD)

Overview

This is a Phase III, multicentre, randomized, double-blind, placebo-controlled, interventional study designed to evaluate the efficacy and safety of a standardized fraction of Picrorhiza kurroa Royal Ex Benth (Picroliv®) in adults with Non-Alcoholic Fatty Liver Disease (NAFLD). A total of 170 adults aged 18-60 years with uncomplicated NAFLD (fibrosis stage up to F2) 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 a treatment duration of 24 weeks. Standard of care includes dietary and lifestyle modifications, exercise recommendations, and management of comorbid conditions as per routine clinical practice. The study aims to assess the efficacy of Picroliv in improving hepatic and metabolic parameters and to evaluate its safety profile compared with placebo. Participants will be followed for a total study duration of 48 weeks. The trial will be conducted across six clinical sites in India.

Detailed description

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.

Interventions

• Drug Picroliv
  Participants will receive Picroliv 100 mg capsules twice daily (after meals) for 24 weeks, in addition to standard of care, which includes dietary counseling, exercise recommendations, and management of comorbid conditions as per routine clinical practice.
• Other Placebo
  Participants will receive matching placebo capsules twice daily (after meals) for 24 weeks, in addition to standard of care, which includes dietary counseling, exercise recommendations, and management of comorbid conditions as per routine clinical practice.

Primary outcome measures

• Change in hepatic fat fraction [Time frame: Baseline to Week 24]

Secondary outcome measures (12)

• Change in liver stiffness [Time frame: Baseline to Week 24]
• Change in Serum Alanine Aminotransferase (ALT) [Time frame: Baseline to Week 24]
• Change in Fasting Plasma Glucose [Time frame: Baseline to Week 24]
• Change in fibrosis score [Time frame: Baseline to Week 24]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: Baseline to Week 48]
• Change in Serum Aspartate Aminotransferase (AST) [Time frame: Baseline to Week 24]
• Change in Glycated Hemoglobin (HbA1c) [Time frame: Baseline to Week 24]
• Change in Total Cholesterol [Time frame: Baseline to Week 24]
• Change in Low-Density Lipoprotein Cholesterol (LDL-C) [Time frame: Baseline to Week 24]
• Change in High-Density Lipoprotein Cholesterol (HDL-C) [Time frame: Baseline to Week 24]
• Change in Triglycerides [Time frame: Baseline to Week 24]
• Severity of Treatment-Emergent Adverse Events (TEAEs) [Time frame: Baseline to Week 48]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

India · 6 centers

• PGIMER — Chandigarh
• Nizam's Institute of Medical Sciences — Panjagutta
• King George 's Medical University — Chowk
• King Edward Memorial Hospital — Mumbai
• All India Institute of Medical Sciences — Delhi
• Institute of Liver and Biliary Sciences — Vasant Kunj

Identifiers

NCT: NCT07452744 · BIAG-CSP-063 · CDRI-ICMR-6/2021

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗