Efficacy and Safety of Tocovid Suprabio 200mg in Non-alcoholic Fatty Liver (NAFL) (T3-NAFL)

A Randomized, Double-Blind, Placebo-Controlled Study, to Assess the Efficacy and Safety of Tocovid Suprabio 200mg in Non-alcoholic Fatty Liver (NAFL)

Palm-derived tocotrienols have shown hepatoprotective effects in both animal and human studies. This study aims to investigate the effects of tocotrienols in hepatocellular lipid content using MRI. Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases ranging from simple fatty liver (steatosis, NAFL) to non-alcoholic steatohepatitis (NASH) to cirrhosis. NASH is the accumulation of fat in liver cells accompanied with inflammation that can lead to the scarring of the liver. Prevention of liver fibrosis by early introduction of low risk interventions such as lifestyle modification, diet control and nutraceuticals may help circumvent long-term healthcare costs associated with management of chronic NASH.

Study Overview

• Status: Completed
• Conditions: NAFLD; Hepatic Steatosis
• Intervention / Treatment: Drug: Tocotrienols / Vitamin E; Drug: Placebo control

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 2

Contacts and Locations

Study Locations

• Malaysia
  • Penang
    • Pulau Pinang, Penang, Malaysia, 11500
      • KK Bandar Baru Air Itam
    • Pulau Pinang, Penang, Malaysia, 11600
      • KK Jalan Perak
    • Pulau Pinang, Penang, Malaysia, 11950
      • KK Bayan Baru
    • Seberang Jaya, Penang, Malaysia, 13700
      • Hospital Seberang Jaya (CRC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 to 70 years old.
2. Diagnosis of non-alcoholic fatty liver (NAFL, hepatic steatosis), using ultrasound or Fibroscan
3. Willing to provide written informed consent

Exclusion Criteria:

1. History or evidence of medical condition(s) associated with chronic liver disease other than NAFL
2. Known history or other evidence of decompensated liver disease (Child-Pugh Grade B or higher), coagulopathy, hyperbilirubinemia, hepatic encephalopathy, hypoalbuminemia, ascites, hepatic encephalopathy, and bleeding from esophageal varices are conditions consistent with decompensated liver disease.

3. Documented underlying medical conditions which may affect assessment or follow-up as listed:

   • Any malignancies
   • eGFR < 60
   • Severe dementia or psychosis
   • Requirement of long-term corticosteroid treatment for the underlying disease such as connective tissue disease
   • Uncontrolled Hemoglobinopathy or anemia
   • Uncontrolled Hyperthyroidism or Hypothyroidism
   • Hemochromatosis
   • Hepatobiliary disorders
   • Participant underwent splenectomy or suffered from splenomegaly
   • Hepatitis B or C
4. History of drug or substance abuse.
5. Estimated alcohol consumption of more than 20 g/day (1 standard drink/day) for women or more than 30 g/day (2 standard drinks/day) for men for at least 6 months prior to enrollment, binge drinking behavior or Alcohol Use and Disorders Identification Test (AUDIT) score of 7 or more
6. History of taking medications known to cause liver impairment such as systemic glucocorticoids, tetracyclines, anabolic steroids, valproic acid, or other known hepatotoxins within 3 months prior to study enrollment
7. History of major organ transplantation with an existing functional graft.
8. Present with signs of acute infection or inflammation at Screening
9. Has medical conditions or recent procedures that do not allow for magnetic resonance (MR) assessments
10. Pregnant, breast feeding, or female of childbearing potential (unless the participant is on effective contraception methods or underwent bilateral tubal ligation, bilateral oophorectomy or hysterectomy previously)
11. Participation in any other interventional trial within the previous three months. Participants enrolled in this study cannot be enrolled in another study for either research, diagnostic or treatment purposes.
12. Known history of severe allergy or immunologically mediated disease (e.g., vasculitis, cryoglobulinemia, inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis requiring more than intermittent nonsteroidal anti-inflammatory medications for management, etc.)
13. New treatment with liver-protective supplements such as S-adenosyl methionine (SAM-e), Ursodeoxycholic acid (UDCA), betain, milk thistle (silymarin), soybean phospholipids (EssentialE®), or fish oil, within 1 month prior to study enrollment.
14. Treatment with vitamin E tocopherol (at dosage more than 50mg/day) or tocotrienols within 1 month prior to enrollment.
15. Treatment using new anti-lipidemic or anti-diabetic agents within 3 months prior to study enrollment.
16. Participant having lesions with a propensity to bleed (e.g., bleeding peptic ulcers) and those having a history of hemorrhagic stroke and those with inherited bleeding disorders (e.g., hemophilia) or patients on warfarin.
17. Elevation of AST or ALT greater than five times upper limit normal (ULN), approximately 250 IU/L, or alkaline phosphatase more than two times ULN (250-300 IU/L).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo control; Placebo matching Tocovid Suprabio; Other Names: Placebo capsule
Active Comparator: Active; Tocovid Suprabio 200mg	Drug: Tocotrienols / Vitamin E; Palm Tocotrienols complex; Other Names: Tocovid Suprabio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of Liver Fat (VLFF)	Between group difference in the proportion of patients with ≥ 30% reduction of baseline of liver fat by Magnetic Resonance Imaging - Volumetric Liver Fat Fraction (MRI-VLFF)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in liver biochemistry	Between group difference in mean change of liver biochemistries (ALT, AST, GGT, AP, Bilirubin)	12 months
Change in liver fat fraction	Between group difference in mean change (%) from Baseline to 12 months in hepatic fat fraction by MRI-VLFF	12 months
Change in serum lipid profile	Between group difference in mean change of serum lipid profile	12 months
Occurrence of adverse events and serious adverse events	Between group difference in the occurrence of adverse events and serious adverse events.	12 months

Collaborators and Investigators

• Sponsor: Yuen Kah Hay
• Collaborators: Monash University Malaysia; Hovid Berhad
• Investigators: Study Chair: Kah Hay Yuen, PhD, Universiti Sains Malaysia

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): August 15, 2023
• Study Completion (Actual): October 1, 2023

Study Registration Dates

• First Submitted: January 7, 2021
• First Submitted That Met QC Criteria: January 7, 2021
• First Posted (Actual): January 11, 2021

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Vitamin E; NAFLD; Hepatic Steatosis; Fatty Liver; Tocotrienols; Palm tocotrienol complex
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin E; Tocopherols; Tocotrienols; Tocovid
• Other Study ID Numbers: T3-NAFL-01-2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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