The Effect of Palm Tocotrienol Rich Fraction on Alcoholic Fatty Liver Disease (AFLD): A Phase II Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Change from baseline in Aspartate Aminotransferase (AST) at 3 and 6 months
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Treatment group (mixed tocotrienol)
The treatment group will be prescribed with palm tocotrienol soft gel capsules (200 mg twice daily) for six months
干预措施: Palm Tocotrienol Rich Fraction (TRF) (Dietary Supplement)
Placebo group
The placebo group will receive refined, bleached, and deodorised (RBD) palm olein for six months.
干预措施: Refined, bleached, and deodorised (RBD) palm olein (Other)
结局指标
主要结局
Change from baseline in Aspartate Aminotransferase (AST) at 3 and 6 months
时间窗: From enrollment to the end of treatment at 3 and 6 months post intervention
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.
Change from baseline in Alanine Aminotransferase (ALT) at 3 and 6 months
时间窗: From enrollment to the end of treatment at 3 and 6 months post intervention.
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.
Change from baseline in Gamma-Glutamyl Transferase (GGT) at 3 and 6 months
时间窗: From enrollment to the end of treatment at 3 and 6 months post intervention.
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.
Between-group difference in AST at 3 and 6 months (Tocotrienol-Rich Fraction [TRF] vs placebo)
时间窗: From enrollment to the end of treatment at 3 and 6 months post intervention
Measured in units per liter (U/L); Lower values indicate improvement.
Between-group difference in ALT at 3 and 6 months (TRF vs placebo)
时间窗: From enrollment to the end of treatment at 3 and 6 months post intervention
Measured in units per liter (U/L); Lower values indicate improvement.
Between-group difference in GGT at 3 and 6 months (TRF vs placebo)
时间窗: From enrollment to the end of treatment at 3 and 6 months post intervention
Measured in units per liter (U/L); Lower values indicate improvement.
Change from baseline in Fatty Liver Index (FLI) at 3 and 6 months
时间窗: From enrollment to the end of treatment at 3 and 6 months post intervention
Unitless score (range 0-100); Reported as absolute and percentage change; Higher scores indicate greater hepatic steatosis (worse outcome).
Between-group difference in Fatty Liver Index (FLI) at 3 and 6 months (TRF vs placebo).
时间窗: From enrollment to the end of treatment at 3 and 6 months post intervention
Range 0-100; Higher scores indicate worse steatosis.
Change from baseline in Liver Stiffness Measurement using Transient Elastography (FibroScan® score) at 3 and 6 months
时间窗: From enrollment to the end of treatment at 3 and 6 months post intervention
Measured in kilopascals (kPa; typical range 2-75); Reported as absolute and percentage change; Higher values indicate greater fibrosis (worse outcome).
Between-group difference in Liver Stiffness Measurement (FibroScan® score) at 3 and 6 months (TRF vs placebo)
时间窗: From enrollment to the end of treatment at 3 and 6 months post intervention
Measured in kilopascals (kPa; typical range 2-75); Higher values indicate worse fibrosis.
次要结局
- 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)
- Change From Baseline in Triglyceride (TG) Concentration at 3 and 6 months.(From enrollment to the end of treatment at 3 and 6 months post intervention)