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

Official title

The Effect of Palm Tocotrienol Rich Fraction on Alcoholic Fatty Liver Disease (AFLD): A Phase II Clinical Trial

Overview

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.

Detailed description

Recent evidence from preclinical studies has shown that tocotrienols, a unique form of Vitamin E derived from palm oil, possess strong antioxidant, anti-inflammatory, and hepatoprotective properties. These effects have been demonstrated in non-alcoholic fatty liver disease (NAFLD) models, suggesting their potential benefit in alcohol-related liver injury as well. However, clinical evidence in human AFLD populations remains limited. Therefore, this study seeks to investigate the efficacy and safety of palm tocotrienol-rich fraction supplementation in patients with AFLD.

This is a randomized, double-blind, placebo-controlled Phase II clinical trial involving 26 adult participants aged 18 to 65 years who have been clinically diagnosed with alcoholic fatty liver disease. Participants will be randomly assigned to either: Treatment group (n = 13): receiving palm tocotrienol-rich fraction soft gels (200 mg twice daily); or Placebo group (n = 13): receiving refined, bleached, and deodorised (RBD) palm olein soft gels (200 mg twice daily). The intervention period will last six months, with follow-up assessments every three months. Participants will complete structured questionnaires on alcohol consumption patterns, lifestyle, and dietary habits at each visit. Blood samples will be collected at baseline and follow-up visits to evaluate liver function tests (ALT, AST, GGT, ALP, bilirubin), oxidative stress markers, haematological parameters, and inflammatory biomarkers such as cytokines. Non-invasive liver assessments, including FibroScan and FibroTest, will be performed twice during the study to monitor changes in liver fat content, and stiffness levels.

This study aims to provide scientific evidence on the efficacy of tocotrienol-rich fraction in improving liver health among individuals with AFLD. If proven effective, tocotrienol may represent a safe therapeutic option for mitigating alcohol-induced liver injury. The findings will also contribute to the development of evidence-based nutraceutical applications of palm tocotrienol and support efforts to diversify and add value to Malaysia's palm oil industry through health-promoting innovations. Moreover, the results will serve as baseline data for larger-scale clinical trials and future research into tocotrienol's broader therapeutic potential.

Interventions

• Dietary supplement Palm Tocotrienol Rich Fraction (TRF)
  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.
• Other Refined, bleached, and deodorised (RBD) palm olein
  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.

Primary outcome measures

• Change from baseline in Aspartate Aminotransferase (AST) at 3 and 6 months [Time frame: 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 [Time frame: 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 [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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 [Time frame: 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). [Time frame: 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 [Time frame: 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) [Time frame: From enrollment to the end of treatment at 3 and 6 months post intervention]

Secondary outcome measures (6)

• Change From Baseline in Plasma Cytokine Levels (Anti-inflammatory Effect of Tocotrienols) at 3 and 6 months. [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: From enrollment to the end of treatment at 3 and 6 months post intervention]
• Change From Baseline in Triglyceride (TG) Concentration at 3 and 6 months. [Time frame: From enrollment to the end of treatment at 3 and 6 months post intervention]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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
• Patients who are judged by investigator that participation of the study is difficult due to disease as follow; hepatic cirrhosis, Wilson's disease, malignant tumor, serious metabolic disease, severe renal disease, severe pulmonary disease, severe cardiovascular disease, severe nervous disease/psychiatric disorder, muscle disease and etc.
• Patients taking vitamin E, herbal supplements, or other investigational products within 90 days prior to the participation in the study.
• Patients who have been taken any medications that could affect the treatment: hypoglycemic agents, colchicine, penicillamine, corticosteroids, ursodeoxycholic acid, pentoxifylline, long-term use of NSAIDs, statins, neuroleptics, anticonvulsant medications, high-dose acetaminophen(>=2.5g/day)
• Patients who have received treatment that may affect liver function within 1 month prior to the participation in the study
• Patients who could not comply with alcohol abstinence.
• Patient who considered ineligible for participation in the study as Investigator's judgment

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

Quadruple blind

Primary purpose

Treatment

Study locations

Malaysia · 1 center

• Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar — Cheras

Publications

• 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, R

Identifiers

NCT: NCT07466485 · JEP-2021-694 · TAP-K010316

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗