Liver Trial on Oral Tocotrienol

Overview

The purpose of this Phase IIA trial is to validate the outcome observed in the Phase I trial that oral TCT attenuates the rise in MELD over time in patients diagnosed with NAFLD, NASH or chronically infected hepatitis C. Subjects will participate for 3 years. They will be asked to come to 8 total study visits and will receive 6 follow-up phone calls within the 3 years of participation. Subjects will be asked to take 2 study capsules of vitamin E Tocotrienol (200mg) twice a day or 2 placebo capsules twice a day. The study is randomized and study staff will be blinded to randomization.

Full Title of Study: “Tocotrienol Against the Progression of End Stage Liver Disease”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: February 2022

Detailed Description

As a safe and natural vitamin, tocotrienol (TCT) stands uniquely poised to treat ~500 million worldwide who suffer from viral hepatitis. Furthermore, for those awaiting liver transplantation, TCT may buy more time until a liver becomes available. The primary purpose of this Phase IIA trial is to validate the outcome observed in the limited sample size Phase I trial (n=6) that oral TCT attenuates the rise in MELD over time in patients with NAFLD, NASH, or Hepatitis C. Outcomes will direct the design of a multi-center Phase IIB trial.

Study participation will last 3 years. Subjects will be seen for an initial visit, at which consent will be obtained and baseline labs drawn, followed by a Randomization visit 2-14 days later after MELD criteria have been confirmed. If the acceptable labs have not been drawn per standard of care to calculate a MELD score within 90 days before the initial visit, the subject will complete the initial visit as planned, but will then return for a repeat lab draw 60 days later to confirm MELD criteria for eligibility before continuing to the randomization visit.

Enrollment occurs when a subject meets all criteria and is randomized into one of the treatment groups. Subjects will then be seen in the research office by research personnel at 1 month, 2 months, 3 months, 6 months, 1 year, 18 months, 2 years, and 3 years. Subjects will receive follow-up phone calls at 9 months, 15 months, 21 months, 27 months, 30 months, and 33 months. Subject compliance with supplements will be closely followed, as compliance is critical for accurate data. Given the small sample size, subjects who are less than 75% compliant at two consecutive study visits will be discontinued from the study. Subjects will be discontinued if their MELD score increases by more than 25% between 2 consecutive visits or if they receive an organ transplant. Subjects will be declared lost to follow-up (LTFU) if a study visit is unable to be scheduled and completed after 4 documented attempts to contact a subject with no response. In this circumstance, a certified letter will be mailed to the subject's last known address; if no response is received, the subject is LTFU. All subjects discontinued or LTFU before the end of 1 year of study participation will be replaced (see protocol to review study visit activities that will occur). At the Randomization Visit, enrolled subjects will be randomized into one of two treatment groups in a 1:1 manner. Group 1: Placebo vehicle; (2) placebo capsules following AM meal, (2) placebo capsules following PM meal Group 2: 800mg TCT; (2) 200mg TCT capsules following AM meal, (2) 200mg TCT capsules following PM meal

Interventions

  • Drug: Tocotrienol
    • Vitamin E is a dietary supplement. Vitamin E is a fat-soluble vitamin that exists in eight different forms. Each form has its own biological activity, which is the measure of potency or functional use in the body. Vitamin E is a dietary antioxidant that assists in maintaining cell integrity. It is obtained from sunflower, safflower, canola, and olive oils; also from many grains, nuts, fruits as well as fatty parts of meats. The tocotrienol form of natural vitamin E is found in rice and cereals but more abundantly in palm oil. Palm oil is an integral part of daily diet in southeastern Asia
  • Other: Placebo
    • Control study capsule that includes no study product (Vitamin E – Tocotrienol)

Arms, Groups and Cohorts

  • Placebo Vehicle
    • Subjects will take 2 placebo capsules following AM meal, 2 placebo capsules following PM capsules
  • Tocotrienol supplement
    • Subjects will take (2) 200 mg TCT capsules following AM meal, (2) 200 mg TCT following PM meal

Clinical Trial Outcome Measures

Primary Measures

  • Effect of Oral tocotrienols (TCT) on Model for End-Stage Liver Disease (MELD) score
    • Time Frame: 3 years
    • Lab tests including viral load viral, viral genotype, bilirubmin, fibrosure, and INR will be taken at baseline study visit and the last study visit ( Study visit 8 – 3 years) and will calculate MELD scores to see if Oral TCT will significantly attenuate the rise in MELD score over time in patients with End Stage Liver Disease

Participating in This Clinical Trial

Inclusion Criteria

  • Age 18 years of above, male or female
  • ESLD patients with clinically- diagnosed NAFLD, NASH, or chronically infected with hepatitis C virus (HCV, all genotypes), with amount of virus in the blood greater than 10,000 IU/ml
  • Absence of any other possible cause for liver dysfunction
  • Stable MELD score of at least 8, but no greater than 15 over the past 6 months (+/- 1 month) prior to enrollment
  • Able to speak and understand English
  • Willing and able to provide informed consent
  • Willing and able to return for regularly scheduled research study visits & comply with study requirements

Exclusion Criteria

  • Rapid deterioration of liver function, over the past 6 months (+/- 1 month) prior to enrollment per study physician determination
  • Hepatocellular carcinoma
  • Positive HIV/ AIDS, or other chronic immunodeficiency
  • Concurrent hepatitis A or B infection
  • Current drug and/or alcohol abuse (per treating physician)
  • Bacterial infection at time of enrollment
  • Daily use of dedicated vitamin E supplementation within the 12 months prior to study participation
  • Platelets <25,000 cells/µL, neutrophils <1000 cells/µL, hemoglobin <8g/dL, total bilirubin >3mg/dL, serum creatinine >2.0mg/dL
  • Women who are pregnant, breastfeeding, or plan to become pregnant during course of study participation (36 months)
  • Other significant comorbidities which limit the subject's life expectancy to less than 36 months
  • Patients receiving medications known to treat Hepatitis C; patients who begin taking these medications during the course of study participation will be dropped.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Indiana University
  • Collaborator
    • Malaysia Palm Oil Board
  • Provider of Information About this Clinical Study
    • Principal Investigator: Chandan Sen, Professor – Indiana University
  • Overall Official(s)
    • Chandan K Sen, Ph.D, Principal Investigator, The Ohio State University Wexner Medical Center
  • Overall Contact(s)
    • Jennifer Mohnacky, RN, 317-278-2715, jmohnack@iu.edu

References

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