Tocotrienol Against the Progression of End Stage Liver Disease
Tocotrienol Against the Progression of End Stage Liver Disease
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.
Tocotrienol (TCT) is a natural vitamin E supplement with a long history of safe dietary
 consumption. Prior studies with Vitamin E have shown beneficial effects in patients with
 non-alcoholic fatty liver disease and cirrhosis. The primary purpose of this Phase 2 trial is
 to validate the outcome observed in an earlier trial that oral TCT attenuates the rise in
 MELD (Model For End-Stage Liver Disease) score over time in patients with cirrhosis. Outcomes
 of this trail will direct the design of a future larger multi-center 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 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 6 months, 1 year, 18 months, 2 years,
 and 3 years. 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.
Inclusion Criteria:

 -  Age 18 years of above, male or female

 -  ESLD patients with clinically- diagnosed NAFLD or NASH

 -  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.