Clinical trial NCT06596382: Tocotrienol as a Treatment for Non-alcoholic Fatty Liver Disease
Official title: A Randomised Double-blind Controlled Trial on Tocotrienol as a Treatment for Non-alcoholic Fatty Liver
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-Alcoholic Fatty Liver Disease
Keywords: Tocotrienol
Vitamin E
Fatty Liver
Lead sponsor: National University of Malaysia
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized double-blinded placebo-controlled trial was performed toward patients diagnosed with NALFD with several established inclusion and exclusion criteria of study. Two main groups were formed to separate the patient into metabolic syndrome and non-metabolic group. In these groups, it will further divided into two groups where the administration of tocotrienol rich-vitamin E and placebo were given in random manner. Each participant will consume the vitamin/placebo daily for one capsule in the duration of six months. Various assessments was conducted before and after taking the vitamin E/placebo.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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

Eligibility criteria: 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.

Primary outcomes:
measure: Fat percentage before and after intervention in percentage
timeFrame: 6 months
measure: Fat free mass in kilogram before and after intervention
timeFrame: 6 months
measure: Basal metabolic rate in kJ before and after intervention
timeFrame: 6 months
measure: Body Mass Index in kg/m2 before and after intervention
timeFrame: 6 months
measure: Visceral fat before and after intervention
timeFrame: 6 months
measure: Liver stiffness based on CAP score before and after intervention
timeFrame: 6 months
measure: Fatty changes in kPA before and after intervention
timeFrame: 6 months
measure: Fibrosis via Fibrotest before and after intervention
timeFrame: 6 months
measure: Inflammation ActiTest before and after intervention
timeFrame: 6 months
measure: Steatosis via SteatoTest before and after intervention
timeFrame: 6 months
measure: mRNA gene expression level of inflammatory cytokines before and after intervention
timeFrame: 6 months
measure: DNA damage analysis via Comet assay before and after intervention
timeFrame: 6 months
Secondary outcomes:
measure: Plasma Protein
timeFrame: 6 months
measure: Liver enzymes
timeFrame: 6 months
measure: Triglyceride levels
timeFrame: 6 months
measure: Fasting glucose levels
timeFrame: 6 months
measure: Total cholesterol levels
timeFrame: 6 months
measure: International Physical Activity Questionnaire (IPAQ)
timeFrame: 6 months
measure: Food Frequency Questionnaire (FFQ)
timeFrame: 6 months
Other outcomes:
Locations:
city: Cheras
country: Malaysia
facility: Hospital Canselor Tuanku Muhriz UKM
state: Wilayah Persekutuan Kuala Lumpur
Study officials:
References: