Tocotrienol as a Treatment for Non-alcoholic Fatty Liver Disease

National University of Malaysia

Status: Completed

Conditions: Non-Alcoholic Fatty Liver Disease

Treatments: Dietary Supplement: Tocotrienol rich-vitamin E; Dietary Supplement: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06596382

FF-2020-180 (Other Grant/Funding Number)

UKM PPI/111/8/JEP-2020-190

Details and patient eligibility

About

Vitamin E's potential in treating non-alcoholic fatty liver disease (NAFLD) is attributed to its antioxidant properties. While tocopherols have shown significant results in NAFLD management, the powerful properties of tocotrienols, another form of saturated vitamin E, remain understudied. This research aims to assess tocotrienol's effectiveness in treating NAFLD, expanding our understanding of its therapeutic benefits.

Full description

This is a randomized double-blinded placebo-controlled trial targeted toward patients being diagnosed with non-alcoholic fatty liver disease. Patients will be screened and identified from the gastroenterology and hepatology clinic in Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur. The study expects a total of 264 participants to take part in this four-arm investigation, requiring a sample size of 66 for each arm, with an alpha probability of 0.05 and a power of 0.8.

The selection of participants is based on established criteria. The criteria include being 18 years and above, having a high CAP score from FibroScan, and elevated ALT levels. Patients with chronic liver diseases, acute disorders affecting the liver, biliary disease, cancer, and liver cirrhosis were excluded. Alcohol intake was monitored, with a minimum amount set. Any history of bariatric surgery deemed participants unfit for the study. Additionally, participants must be free from the use of steatogenic medication, antibiotics/probiotics, and lipid-lowering agents within one to three months before the study.

After the screening process, participants were assigned to two groups based on metabolic syndrome presence. Within each group, individuals were randomly selected to receive either a vitamin E supplement or a placebo. Each vitamin E capsule contains a certain amount of dosage with a safe concentration for consumption. The metabolic group received 100mg of tocotrienol rich-vitamin E, while the non-metabolic group received 50mg of tocotrienol rich-vitamin E. Meanwhile, each placebo capsule does not contain any vitamin E, which supplied to both group.

Several analyses were performed before and after vitamin E/placebo administration. Firstly, anthropometric data was gathered for their physical measurement. Besides that, FibroScan and LiverFast analysis to examine the liver health condition. Other than that,molecular approach was also conducted to assess the mRNA gene expression level on the selected cytokines such as TNFα, IFNγ, IL-6, and IL-8 and also observe the DNA damage of the cells using Comet Assay. Additionally, biochemical blood testing was tested on 10 parameters to measure its concentration levels within the body. Lastly, each participant was required to answer questionnaires for evaluation on physical activity levels via IPAQ and their dietary patterns through the FFQ

Enrollment: 264 patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of NAFLD is confirmed by the presence of fatty liver detected by abdominal ultrasound and controlled attenuation parameter (CAP) score from FibroScan® of >263 dB/m
• Raised ALT level (above the upper limit of normal): >35 U/L for males and >25 U/L for females

Exclusion criteria

• Evidence of other chronic liver diseases (e.g. Hepatitis B, C infections, autoimmune hepatic disorders)
• Evidence of acute disorders affecting the liver (e.g. drug-induced liver injury, non-Hepatitis B, C viral infection)
• Biliary disease
• Liver cancer - primary hepatocellular carcinoma or liver metastasis
• Evidence of liver cirrhosis
• Alcohol intake of >20 g/day for males and 10 g/day for females
• Use of steatogenic medications within the past three months (e.g. systemic steroids, methotrexate)
• History of bariatric surgery
• Intake of antibiotics and/or probiotic supplements within two months prior to the study
• Intake of a lipid-lowering agent (statin) within a month prior to the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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264 participants in 4 patient groups, including a placebo group

NAFLD with metabolic syndrome; intervention with tocotrienol rich-vitamin E

Active Comparator group

Description:

66 patient diagnosed with NALFD and associated with metabolic syndrome were given 100mg of tocotrienol rich-vitamin E for six months

Treatment:

Dietary Supplement: Tocotrienol rich-vitamin E

NAFLD without metabolic syndrome; intervention with tocotrienol rich-vitamin E

Active Comparator group

Description:

66 patient diagnosed with NALFD without being associated with metabolic syndrome were given 50mg of tocotrienol rich-vitamin E for six months

Treatment:

Dietary Supplement: Tocotrienol rich-vitamin E

NAFLD with metabolic syndrome; intervention with placebo

Placebo Comparator group

Description:

66 patient diagnosed with NALFD and associated with metabolic syndrome were given placebo for six months

Treatment:

Dietary Supplement: Placebo

NAFLD without metabolic syndrome; intervention with placebo

Placebo Comparator group

Description:

66 patient diagnosed with NALFD without being associated with metabolic syndrome were given placebo for six months

Treatment:

Dietary Supplement: Placebo