The Efficacy of Tocotrienol Rich Fraction for Liver Protection in Adult Patients With Alcoholic Fatty Liver Disease (AFLD)

NCT07466485 | Not Yet Recruiting Phase 2

• 2 other identifiers: JEP-2021-694TAP-K010316
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical study aims to explore the potential liver-protective effects of palm tocotrienol-rich fraction (a form of Vitamin E) in adults with alcoholic fatty liver disease (AFLD). A total of 26 participants aged 18 to 65 years with AFLD will be randomly assigned to receive either tocotrienol (200 mg twice daily) or a placebo for six months. Throughout the study, participants will undergo regular liver health assessments including blood tests, FibroScan, and FibroTest, alongside evaluations of oxidative stress and inflammation markers. The study aims to determine whether tocotrienol can help improve liver function and reduce alcohol-related liver damage. Findings from this trial may provide valuable evidence for future clinical studies and highlight the potential of Malaysian palm-based tocotrienol as a natural, supportive approach to liver health.

Conditions

Alcoholic Fatty Liver Disease

Keywords

Liver diseases; Tocotrienols; Antioxidants; Oxidative stress

Outcome Measures

Primary Outcomes (10)

• Change from baseline in Aspartate Aminotransferase (AST) at 3 and 6 months

  Reported as absolute and percentage change; Measured in units per liter (U/L); Typical range: 8-48 U/L; Lower values indicate improved liver function.

  From enrollment to the end of treatment at 3 and 6 months post intervention

• Change from baseline in Alanine Aminotransferase (ALT) at 3 and 6 months

  Reported as absolute and percentage change; Measured in units per liter (U/L); Typical ranges: 7-56 U/L; Lower values indicate improved liver function.

  From enrollment to the end of treatment at 3 and 6 months post intervention.

• Change from baseline in Gamma-Glutamyl Transferase (GGT) at 3 and 6 months

  Reported as absolute and percentage change; Measured in units per liter (U/L); Typical ranges: 8 - 61 U/L; Lower values indicate improved liver function.

  From enrollment to the end of treatment at 3 and 6 months post intervention.

• Between-group difference in AST at 3 and 6 months (Tocotrienol-Rich Fraction [TRF] vs placebo)

  Measured in units per liter (U/L); Lower values indicate improvement.

  From enrollment to the end of treatment at 3 and 6 months post intervention

• Between-group difference in ALT at 3 and 6 months (TRF vs placebo)

  Measured in units per liter (U/L); Lower values indicate improvement.

  From enrollment to the end of treatment at 3 and 6 months post intervention

• Between-group difference in GGT at 3 and 6 months (TRF vs placebo)

  Measured in units per liter (U/L); Lower values indicate improvement.

  From enrollment to the end of treatment at 3 and 6 months post intervention

• Change from baseline in Fatty Liver Index (FLI) at 3 and 6 months

  Unitless score (range 0-100); Reported as absolute and percentage change; Higher scores indicate greater hepatic steatosis (worse outcome).

  From enrollment to the end of treatment at 3 and 6 months post intervention

• Between-group difference in Fatty Liver Index (FLI) at 3 and 6 months (TRF vs placebo).

  Range 0-100; Higher scores indicate worse steatosis.

  From enrollment to the end of treatment at 3 and 6 months post intervention

• Change from baseline in Liver Stiffness Measurement using Transient Elastography (FibroScan® score) at 3 and 6 months

  Measured in kilopascals (kPa; typical range 2-75); Reported as absolute and percentage change; Higher values indicate greater fibrosis (worse outcome).

  From enrollment to the end of treatment at 3 and 6 months post intervention

• Between-group difference in Liver Stiffness Measurement (FibroScan® score) at 3 and 6 months (TRF vs placebo)

  Measured in kilopascals (kPa; typical range 2-75); Higher values indicate worse fibrosis.

  From enrollment to the end of treatment at 3 and 6 months post intervention

Secondary Outcomes (6)

• Change From Baseline in Plasma Cytokine Levels (Anti-inflammatory Effect of Tocotrienols) at 3 and 6 months.

  From enrollment to the end of treatment at 3 and 6 months post intervention

• Change From Baseline in Fasting Blood Glucose [FBG] Concentration at 3 and 6 months

  From enrollment to the end of treatment at 3 and 6 months post intervention

• Change From Baseline in Total Cholesterol (TC) Concentration at 3 and 6 months

  From enrollment to the end of treatment at 3 and 6 months post intervention

• Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) Concentration at 3 and 6 months

  From enrollment to the end of treatment at 3 and 6 months post intervention

• Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) Concentration at 3 and 6 months

  From enrollment to the end of treatment at 3 and 6 months post intervention

Study Arms (2)

Treatment group (mixed tocotrienol)

ACTIVE COMPARATOR

The treatment group will be prescribed with palm tocotrienol soft gel capsules (200 mg twice daily) for six months

Dietary Supplement: Palm Tocotrienol Rich Fraction (TRF)

Placebo group

PLACEBO COMPARATOR

The placebo group will receive refined, bleached, and deodorised (RBD) palm olein for six months.

Other: Refined, bleached, and deodorised (RBD) palm olein

Interventions

Palm Tocotrienol Rich Fraction (TRF) DIETARY_SUPPLEMENT

The treatment group will be prescribed with palm tocotrienol soft gel (200 mg twice daily). The composition of the tocotrienol mixture is 24.7% α-tocotrienol, 4.5% β-tocotrienol, 36.9% γ-tocotrienol, 12.0% σ-tocotrienol and 21.6% α-tocopherol. It is formulated with a self-emulsifying system (SES) to enhance absorption of tocotrienol. One soft gel will be taken orally, daily after breakfast and dinner to complete the 400 mg daily dose. The treatment period will be 6 months.

Treatment group (mixed tocotrienol)

Refined, bleached, and deodorised (RBD) palm olein OTHER

The placebo consisted of an equivalent volume of refined, bleached, and deodorised (RBD) palm olein. The placebo was formulated as soft gelatin capsules that were identical to the tocotrienol capsules in colour, size, shape, and surface texture.

Placebo group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with history of alcoholic use disorder with clinical and biochemical evidence of alcoholic steatohepatitis (AST:ALT \>2.0, elevated GGT)
• Patients with Maddrey's discriminant function ≤ 32, and do not require the treatment of corticosteroid therapy or pentoxifylline.
• Patients aged 18 to 65
• Patients who could comply with alcohol abstinence.

You may not qualify if:

• Severe alcoholic hepatitis defined as Maddrey's discriminant function \>32
• Patients with other concomitant liver diseases:
• Hepatitis B
• Hepatitis C
• Non-alcoholic fatty liver disease (NAFLD)
• Autoimmune hepatitis (AIH)
• Hereditary hemochromatosis
• Patients who are obese (a BMI of 30 kg/ m2 or more) and with metabolic syndromes
• Patients with bleeding disorders and who have been on anticoagulant or antiaggregant treatments
• Patients who have been on corticosteroid therapy or pentoxifylline for alcoholic hepatitis
• Patients with hepatocellular carcinoma
• Pregnant patients
• Patients who are breastfeeding
• Patients with Childs C liver cirrhosis
• Patients who have pyridoxine allergy or history

Sponsors & Collaborators

• Universiti Kebangsaan Malaysia Medical Centre: lead
• Malaysia Palm Oil Board: collaborator
• Hovid Berhad: collaborator

Study Sites (1)

Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak

Cheras, Kuala Lumpur, 56000, Malaysia

Location

Related Publications (1)

• REFERENCES: 1. Liver EAftSot. EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. Journal of hepatology 2018;69: 154-181. 2. Institute for Public Health (IPH), National Institutes of Health, Ministry of Health Malaysia. 2020. National Health and Morbidity Survey (NHMS) 2019: Vol. I: NCDs - NonCommunicable Diseases: Risk Factors and other Health Problems. 3. Chacko KR, Reinus J. Spectrum of alcoholic liver disease. Clinics in liver disease 2016;20: 419-427. 4. Deleuran T, Grønbaek H, Vilstrup H, Jepsen P. Cirrhosis and mortality risks of biopsy- verified alcoholic pure steatosis and steatohepatitis: a nationwide registry-based study. Alimentary pharmacology & therapeutics 2012;35: 1336-1342. 5. Setshedi M, Wands JR, de la Monte SM. Acetaldehyde adducts in alcoholic liver disease. Oxidative medicine and cellular longevity 2010;3. 6. Rolla R, Vay D, Mottaran E, et al. Detection of circulating antibodies against malondialdehyde-acetaldehyde adducts in patients with alcohol-induced liver disease. Hepatology 2000;31: 878-884. 7. Nagata K, Suzuki H, Sakaguchi S. Common pathogenic mechanism in development progression of liver injury caused by non-alcoholic or alcoholic steatohepatitis. J Toxicol Sci. 2007;32(5):453-68. 8. Nath B, Levin I, Csak T, Petrasek J, Mueller C, Kodys K, et al. Hepatocyte-specific hypoxia- inducible factor-1α is a determinant of lipid accumulation and liver injury in alcoholinduced steatosis in mice. Hepatology. 2011;53(5):1526-37. 9. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. (2012) 55:2005-23. 10. European Association for the Study of the Liver, European Association for the Study of Diabetes, European Association for the Study of Obesity. EASL-EASD-EA

  BACKGROUND

MeSH Terms

Conditions

Fatty Liver, Alcoholic; Liver Diseases

Condition Hierarchy (Ancestors)

Fatty Liver; Digestive System Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Study Officials

• Professor Dr. Nur Azlina Mohd Fahami, DVM

  Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Siti Norain Azahar, Medicine (MD)

CONTACT

60-1126792792; drainazahar@gmail.com

Professor Dr. Nur Azlina Mohd Fahami, DVM

CONTACT

+60-391459574; nurazlinamf@ukm.edu.my

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: For the purpose of assigning participants to interventions, each subject was assigned a unique identification number. The researcher who generated the random allocation sequence and assigned participants was masked to the participants' clinical data and was independent of those involved in participant enrolment. Both researchers and participants were masked to the assigned treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a randomised, double-mask, placebo-controlled (parallel group), phase 2 clinical trial investigating the effect of palm tocotrienol-rich fraction on alcoholic fatty liver disease (AFLD).

Study Record Dates

• First Submitted: February 12, 2026
• First Posted: March 12, 2026
• Study Start: May 2, 2026
• Primary Completion (Estimated): November 10, 2026
• Study Completion (Estimated): February 15, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

MY (1)