Tocotrienol for End Stage Liver Disease

Overseen By Kaitlyn Depinet, FNP-C

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Chandan Sen

Must not be taking: Vitamin E

Disqualifiers: Hepatocellular carcinoma, HIV/AIDS, Hepatitis B/C, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 3 years

70 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot participate if you have been taking more than 100 IU of vitamin E daily in the past 3 months.

What data supports the effectiveness of the drug Tocotrienol for End Stage Liver Disease?

Research shows that tocotrienol, a form of vitamin E, can reduce liver inflammation and fibrosis (scarring) in conditions like nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), which suggests it might help with liver issues in end-stage liver disease as well. ^{1 2 3 4 5}

Is tocotrienol safe for humans?

Tocotrienol, a form of vitamin E, has been studied in humans and shown to be transported to vital organs without reported safety issues. It has been used in studies for liver conditions and appears to be safe for human consumption. ^{1 2 3 4 6}

How is tocotrienol different from other treatments for end-stage liver disease?

Tocotrienol is unique because it is a form of vitamin E that can be taken orally and has been shown to lower the model for end-stage liver disease (MELD) score in some patients, which is not commonly achieved by other treatments. It also has potent anti-inflammatory and antioxidant properties that may help protect the liver. ^{1 2 4 6 7}

What is the purpose of this trial?

The purpose of this Phase 2 trial is to validate the outcome observed in a previous trial that oral Tocotrienol (TCT) attenuates the rise in MELD score over time in patients with end stage liver disease / cirrhosis. The study is double blind and participants will be randomized to take 2 capsules of TCT (200mg) or placebo twice a day for 3 years.

Research Team

Raj Vuppalanchi, MD

Principal Investigator

Indiana Unviersity School of Medicine

Chandan K Sen, Ph.D

Principal Investigator

University of Pittsburgh

Eligibility Criteria

Adults with end stage liver disease or cirrhosis, specifically from non-alcoholic fatty liver disease (NAFLD) or NASH, who have a stable MELD score between 8 and 17. Participants must not have other causes for liver dysfunction, no hepatitis B/C or HIV/AIDS, no recent rapid deterioration of liver function, and cannot be pregnant or planning pregnancy.

Inclusion Criteria

Willing and able to provide informed consent

I can attend all required study visits and follow the study rules.

I have end-stage liver disease due to fatty liver.

Exclusion Criteria

Current drug and/or alcohol abuse (per treating physician)

My liver function has worsened quickly, with a significant increase in my MELD score recently.

I have liver cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-14 days

Initial visit, Randomization visit

Treatment

Participants receive either 800mg TCT or placebo capsules twice daily for 3 years

3 years

Visits at 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 6 months, 1 year, 18 months, 2 years, and 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Tocotrienol (TCT)

Trial Overview The trial is testing if Tocotrienol (TCT), taken as two capsules twice daily for three years, can slow down the worsening of the MELD score in patients with advanced liver disease compared to a placebo. The study is double-blind and randomized.

Participant Groups

Group I: Tocotrienol supplement Active Control 1 Intervention

Subjects will take (2) 200 mg TCT capsules following AM meal, (2) 200 mg TCT following PM meal

Group II: Placebo Vehicle Placebo Group 1 Intervention

Subjects will take 2 placebo capsules following AM meal, 2 placebo capsules following PM capsules

Who Is Running the Clinical Trial?

Chandan Sen

Lead Sponsor

Trials

3

Recruited

380+

Indiana University

Collaborator

Trials

1,063

Recruited

1,182,000+

Malaysia Palm Oil Board

Collaborator

Trials

39

Recruited

3,100+

References

1. Germany pubmed.ncbi.nlm.nih.gov

Gamma-Tocotrienol Attenuates the Hepatic Inflammation and Fibrosis by Suppressing Endoplasmic Reticulum Stress in Mice. [2019]

2. Japan pubmed.ncbi.nlm.nih.gov

Effect of tocotrienol on the primary progression of nonalcoholic steatohepatitis in a mouse model. [2022]

3. Scotland pubmed.ncbi.nlm.nih.gov

Comparison of delta-tocotrienol and alpha-tocopherol effects on hepatic steatosis and inflammatory biomarkers in patients with non-alcoholic fatty liver disease: A randomized double-blind active-controlled trial. [2022]

4. Turkey pubmed.ncbi.nlm.nih.gov

Effects of Delta-tocotrienol Supplementation on Liver Enzymes, Inflammation, Oxidative stress and Hepatic Steatosis in Patients with Nonalcoholic Fatty Liver Disease. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Long-term administration of tocotrienols and tumor-marker enzyme activities during hepatocarcinogenesis in rats. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Oral tocotrienols are transported to human tissues and delay the progression of the model for end-stage liver disease score in patients. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Natural vitamin E alpha-tocotrienol: retention in vital organs in response to long-term oral supplementation and withdrawal. [2019]