T3-NAFL: Efficacy and Safety of Tocovid Suprabio 200mg in Non-alcoholic Fatty Liver (NAFL)

Sponsor

Yuen Kah Hay (Other)

Overall Status

Recruiting

CT.gov ID

NCT04704063

Collaborator

Monash University Malaysia (Other), Hovid Berhad (Industry)

170

Enrollment

Locations

Arms

28.9

Anticipated Duration (Months)

42.5

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Palm-derived tocotrienols have shown hepatoprotective effects in both animal and human studies. This study aims to investigate the effects of tocotrienols in hepatocellular lipid content using MRI. Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases ranging from simple fatty liver (steatosis, NAFL) to non-alcoholic steatohepatitis (NASH) to cirrhosis. NASH is the accumulation of fat in liver cells accompanied with inflammation that can lead to the scarring of the liver. Prevention of liver fibrosis by early introduction of low risk interventions such as lifestyle modification, diet control and nutraceuticals may help circumvent long-term healthcare costs associated with management of chronic NASH.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Steatosis NAFLD	Drug: Tocotrienols / Vitamin E Drug: Placebo control	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

170 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Placebo-Controlled Study, to Assess the Efficacy and Safety of Tocovid Suprabio 200mg in Non-alcoholic Fatty Liver (NAFL)

Actual Study Start Date :

Jan 1, 2021

Anticipated Primary Completion Date :

Jan 30, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active Tocovid Suprabio 200mg	Drug: Tocotrienols / Vitamin E Palm Tocotrienols complex Other Names: Tocovid Suprabio
Placebo Comparator: Placebo Placebo	Drug: Placebo control Placebo matching Tocovid Suprabio Other Names: Placebo capsule

Arm

Intervention/Treatment

Active Comparator: Active

Tocovid Suprabio 200mg

Drug: Tocotrienols / Vitamin E

Palm Tocotrienols complex

Other Names:

Tocovid Suprabio

Placebo Comparator: Placebo

Placebo

Drug: Placebo control

Placebo matching Tocovid Suprabio

Other Names:

Placebo capsule

Outcome Measures

Primary Outcome Measures

Reduction of Liver Fat (VLFF) [12 months]
Between group difference in the proportion of patients with ≥ 30% reduction of baseline of liver fat by Magnetic Resonance Imaging - Volumetric Liver Fat Fraction (MRI-VLFF)

Secondary Outcome Measures

Change in liver biochemistry [12 months]
Between group difference in mean change of liver biochemistries (ALT, AST, GGT, AP, Bilirubin)
Change in liver fat fraction [12 months]
Between group difference in mean change (%) from Baseline to 12 months in hepatic fat fraction by MRI-VLFF
Change in serum lipid profile [12 months]
Between group difference in mean change of serum lipid profile
Occurrence of adverse events and serious adverse events [12 months]
Between group difference in the occurrence of adverse events and serious adverse events.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18 to 70 years old.
Diagnosis of non-alcoholic fatty liver (NAFL, hepatic steatosis), using ultrasound or Fibroscan
Willing to provide written informed consent

Exclusion Criteria:

History or evidence of medical condition(s) associated with chronic liver disease other than NAFL
Known history or other evidence of decompensated liver disease (Child-Pugh Grade B or higher), coagulopathy, hyperbilirubinemia, hepatic encephalopathy, hypoalbuminemia, ascites, hepatic encephalopathy, and bleeding from esophageal varices are conditions consistent with decompensated liver disease.
Documented underlying medical conditions which may affect assessment or follow-up as listed:

Any malignancies
eGFR < 60
Severe dementia or psychosis
Requirement of long-term corticosteroid treatment for the underlying disease such as connective tissue disease
Uncontrolled Hemoglobinopathy or anemia
Uncontrolled Hyperthyroidism or Hypothyroidism
Hemochromatosis
Hepatobiliary disorders
Participant underwent splenectomy or suffered from splenomegaly
Hepatitis B or C

History of drug or substance abuse.
Estimated alcohol consumption of more than 20 g/day (1 standard drink/day) for women or more than 30 g/day (2 standard drinks/day) for men for at least 6 months prior to enrollment, binge drinking behavior or Alcohol Use and Disorders Identification Test (AUDIT) score of 7 or more
History of taking medications known to cause liver impairment such as systemic glucocorticoids, tetracyclines, anabolic steroids, valproic acid, or other known hepatotoxins within 3 months prior to study enrollment
History of major organ transplantation with an existing functional graft.
Present with signs of acute infection or inflammation at Screening
Has medical conditions or recent procedures that do not allow for magnetic resonance (MR) assessments
Pregnant, breast feeding, or female of childbearing potential (unless the participant is on effective contraception methods or underwent bilateral tubal ligation, bilateral oophorectomy or hysterectomy previously)
Participation in any other interventional trial within the previous three months. Participants enrolled in this study cannot be enrolled in another study for either research, diagnostic or treatment purposes.
Known history of severe allergy or immunologically mediated disease (e.g., vasculitis, cryoglobulinemia, inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis requiring more than intermittent nonsteroidal anti-inflammatory medications for management, etc.)
New treatment with liver-protective supplements such as S-adenosyl methionine (SAM-e), Ursodeoxycholic acid (UDCA), betain, milk thistle (silymarin), soybean phospholipids (EssentialE®), or fish oil, within 1 month prior to study enrollment.
Treatment with vitamin E tocopherol (at dosage more than 50mg/day) or tocotrienols within 1 month prior to enrollment.
Treatment using new anti-lipidemic or anti-diabetic agents within 3 months prior to study enrollment.
Participant having lesions with a propensity to bleed (e.g., bleeding peptic ulcers) and those having a history of hemorrhagic stroke and those with inherited bleeding disorders (e.g., hemophilia) or patients on warfarin.
Elevation of AST or ALT greater than five times upper limit normal (ULN), approximately 250 IU/L, or alkaline phosphatase more than two times ULN (250-300 IU/L).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	KK Bandar Baru Air Itam	Air Itam	Penang	Malaysia	11500
2	KK Bayan Baru	Bayan Baru	Penang	Malaysia	11950
3	Hospital Seberang Jaya (CRC)	Seberang Jaya	Penang	Malaysia	13700
4	KK Jalan Perak	Penang		Malaysia	11600