None listed
Conditions
Brief summary
Non-alcoholic steatohepatitis (NASH) is an advanced form of non-alcoholic fatty liver disease (NAFLD). NAFLD is caused by a build-up of fat in the liver. This build-up causes inflammation and damage, known as NASH, leading to scarring of the liver and developing the life-threatening condition of cirrhosis. There are no medicines currently approved for the treatment of NASH. Current treatments include dietary changes, weight loss, increased exercise and treatment of associated dyslipidaemia and metabolic syndrome. Recent studies suggest that lifestyle changes (nutritional counselling and exercise) with or without 100mg per day of a mixed tocotrienol product for 3 months showed a decrease in liver stiffness. 79% of those who improved were from the tocotrienol group and 21% from the lifestyle only group. This study will compare treatment with the tocotrienol, TransT3-60, a sublingual powder, to matching placebo, to compare the effects on liver structure measured by ultrasound and magnetic resonance imaging. Safety assessments will be conducted at baseline and 4 weekly intervals. A total of 80 participants will be randomly allocated (1:1) to either the tocotrienol treatment (TransT3-60) or to the placebo group for 24 weeks.
Interventions
60mg tocotrienol (TransT3-60) powder, self-administered sublingually three times daily for 24 weeks.
Supervised administration: The participant will self-administer their first dose on site under the supervision of a qualified study staff member during their first dosing appointment.
Prior to this first dose, participants will be instructed on how to self-administer the powder. This process includes the staff member going through an instruction sheet on how to self-administer the powder, a copy
60mg tocotrienol (TransT3-60) powder, self-administered sublingually three times daily for 24 weeks. Supervised administration: The participant will self-administer their first dose on site under the supervision of a qualified study staff member during their first dosing appointment. Prior to this first dose, participants will be instructed on how to self-administer the powder. This process includes the staff member going through an instruction sheet on how to self-administer the powder, a copy of which will be provided to the participant to take home. The staff member will provide the opportunity for the participant to ask any questions about the administration process if they are unsure. After the first dose, a self-report diary will be provided to the participant to record all subsequent dosing details, as well as any adverse reactions and concomitant medications they may have while on study. The staff member will instruct the participant on how to fill out the diary, and the participant will be able to ask any questions if needed. The diary will include contact details in the event the participant has any questions about self-administration while at home. Study staff will also confirm during subsequent clinic visits that the participant is adhering to the administration requirements.
Sponsors
Invictus Ops Pty Ltd
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age greater than 18 years. 2. Patients will be selected by investigators as likely to have NASH but not cirrhosis, based on the patient’s history, physical examination, imaging and laboratory tests or incidental recent liver biopsy. 3. MRI-PDFF hepatic fat fraction should be >8%. 4. Fibroscan score should indicate NASH and not cirrhosis. 5. Participant must read and understand the informed consent form and must have signed it prior to any study-related procedures being performed. 6. Willingness and ability to comply with all scheduled study visits and study procedures.
Exclusion criteria
1. Chronic hepatitis B and C. Patients who are HCV PCR negative and have been negative for at least 12 months may be included. Patients with HBV on antiviral therapy with a HBV DNA <20 IU/mL for at least 6 months may be included. 2. HIV antibody positive. 3. Concomitant liver disease such as autoimmune hepatitis, primary biliary cirrhosis and Wilson’s disease. 4. Decompensated advanced liver disease and cirrhosis. 5. Treatment with medications known to cause fatty liver such as methotrexate, atypical neuroleptics and tamoxifen. 6. Uncontrolled hypo or hyperthyroidism. 7. Uncontrolled diabetes, HBA1c >9. 8. Active coronary artery disease defined as persisting angina. 9. Chronic kidney disease with an eGFR<60mL/min. 10. Platelet count<100,000/mm3, INR>1.3, ALT>5XULN. 11. Alcohol use >20g/day or substance abuse in the last 12 months. 12. Treatment with insulin sensitisers such as glitazones. 13. Treatment with silymarin (milk thistle). 14. Treatment with vitamin E (tocopherol) in the 4 weeks prior to study entry and for the duration of study participation. 15. Patients who are unable or unwilling to comply with the protocol requirements. 16. Women who are pregnant or lactating at the time of Randomisation. 17. Participation in any investigational study within 8 weeks of screening visit. 18. Participant has any other medical condition that, in the opinion of the investigator and/or medical monitor, would make the participant unsuitable for the study.
Outcome results
None listed