Proliverenol Supplementation for Non-Alcoholic Fatty Liver Disease (NAFLD)

The Effect of Proliverenol Supplementation on Liver Function in Patients With Non-Alcoholic Fatty Liver Disease (NAFLD)

This is a 4-arm, prospective, randomized, double-blind, double-dummy, and placebo-controlled clinical study comparing Proliverenol at a dose of 500 mg twice daily; Proliverenol at a dose of 1000 mg once daily; Proliverenol at a dose of 1000 mg twice daily; and Placebo two caplets daily for a 12-week course of therapy.

Proliverenol is a bioactive fraction derived from the dried fruit of Phaleria macrocarpa (Scheff.) Boerl (Thymelaeaceae). Proliverenol possesses a hepatoprotective activity via anti-inflammation, DNA repairing, and the antiapoptosis properties.

Study Overview

• Status: Completed
• Conditions: Non-Alcoholic Fatty Liver Disease (NAFLD)
• Intervention / Treatment: Drug: Proliverenol; Drug: Placebo caplets of Proliverenol

Detailed Description

There will be 4 groups of treatment; each group will consist of 20 subjects with the treatment regimens for 12 weeks:

Treatment I : 1 caplet of Proliverenol 500 mg twice daily Treatment II : 2 caplets of Proliverenol 500 mg once daily Treatment III : 2 caplets of Proliverenol 500 mg twice daily Treatment IV : 2 caplets of Placebo daily

Study subjects will be asked to come to the clinic every 4-week interval throughout the study period.

Subjects will be evaluated for treatment efficacy at baseline and at interval of 4 weeks over the 12-week course of therapy. Throughout the 12-week therapy, subjects should record the product consumption and adverse event occurred during the study in the provided Patient's Diary.

The safety profile of study medication other than vital signs and adverse event will be measured at baseline and end of study.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Indonesia
  • Jakarta
    • Jakarta Pusat, Jakarta, Indonesia, 10430
      • Division of Hepatology, Dr. Cipto Mangunkusumo Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent
2. Male or female subjects with age of 18 years or older at screening.
3. Diagnosed as NAFLD with liver ultrasonography (USG). Patients with bright liver appearance based on USG, will be followed by CAP examination. Steatosis is defined if CAP >263 dB/m
4. Presence of hepatic impairment, defined as any of serum ALT level > ULN
5. Able to take oral medication.

Exclusion Criteria:

1. Suspected positive COVID-19 based on clinical symptoms or SARS-COV-2 antigen test
2. Pregnancy and lactation period.
3. Suspected alcoholic liver disease
4. History of or presence of autoimmune liver diseases
5. Presence of Bilirubin level > 2x ULN
6. Uncontrolled Diabetes Mellitus with HbA1c ≥ 9.0%
7. History or presence of significant/advanced CV, metabolic, acute or chronic infectious diseases, including viral hepatitis (B and C), or malignancy.
8. Suspected cirrhosis as supported by biochemical profile (PLT count, albumin)
9. Presence of severe renal dysfunction
10. Current or regular use of drug-induced hepatotoxicity, such as: such as non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, anti-epileptic drugs (e.g. carbamazepines, phenytoin, barbiturates), or anti-tuberculous drugs other than the investigational product
11. Current or regular use of herbal medicines with hepato-protective properties
12. Known or suspected hypersensitivity to the trial product or related products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment 1; 1 caplet of Proliverenol 500 mg twice daily	Drug: Proliverenol; 1 caplet of Proliverenol 500 mg twice daily 2 caplets of Proliverenol 500 mg once daily 2 caplets of Proliverenol 500 mg twice daily
Experimental: Treatment 2; 2 caplets of Proliverenol 500 mg once daily	Drug: Proliverenol; 1 caplet of Proliverenol 500 mg twice daily 2 caplets of Proliverenol 500 mg once daily 2 caplets of Proliverenol 500 mg twice daily
Experimental: Treatment 3; 2 caplets of Proliverenol 500 mg twice daily	Drug: Proliverenol; 1 caplet of Proliverenol 500 mg twice daily 2 caplets of Proliverenol 500 mg once daily 2 caplets of Proliverenol 500 mg twice daily
Placebo Comparator: Treatment 4; 2 caplets of Placebo daily	Drug: Placebo caplets of Proliverenol; 2 caplets of Proliverenol Placebo daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of serum ALT levels	Changes of serum ALT levels from baseline to Week 4, 8, and 12 of study treatment	4, 8, and 12 weeks
Changes of serum AST levels	Changes of serum AST levels from baseline to Week 4, 8, and 12 of study treatment	4, 8, and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
USG examination for Controlled Attenuated Parameter (CAP)	USG examination for Controlled Attenuated Parameter (CAP) measurement will be performed on baseline and week 12 of study treatment	0 and 12 weeks
USG examination for Transient elastography (TE)	USG examination for Transient elastography (TE) measurement will be performed on baseline and week 12 of study treatment	0 and 12 weeks
Ratio of Aspartate transaminase (AST) to alanine transaminase (ALT) serum levels	Ratio of Aspartate transaminase (AST) to alanine transaminase (ALT) serum levels at Week 4, 8, and 12 of study treatment	4, 8, and 12 weeks
Liver function (GGT and AP)	Concentration of serum gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (AP) at Baseline and at the End of study	0 and 12 weeks
Liver function (Bilirubin)	Concentration of total bilirubin at Baseline and at the End of study	0 and 12 weeks
Lipid profile (Total cholesterol, LDL, HDL, triglyceride)	Concentration of total cholesterol, LDL, HDL, triglyceride at Baseline and at the End of study	0 and 12 weeks
Renal function (Ureum and creatinine)	Level of ureum and creatinine at Baseline and at the End of study	0 and 12 weeks
Hematology test	Hematology test (especially leucocyte and platelet counts) at Baseline and at the End of study	0 and 12 weeks
Adverse events	Adverse event, will be observed throughout the study conduct	4, 8, and 12 weeks

Collaborators and Investigators

• Sponsor: Dexa Medica Group
• Collaborators: PT Equilab International
• Investigators: Principal Investigator: Irsan D. Hasan, MD, SpPD, KGEH, Division of Hepatology, Departement of Internal Medicine Faculty of Medicine, University of Indonesia Dr. Cipto Mangunkusumo Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2023
• Primary Completion (Actual): August 9, 2024
• Study Completion (Actual): August 28, 2024

Study Registration Dates

• First Submitted: November 7, 2023
• First Submitted That Met QC Criteria: November 7, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: NAFLD; Proliverenol
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: CR.079/EQL/2021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No