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.
- Study Type: Interventional
- Study Design
- Allocation: Randomized
- Intervention Model: Single Group Assignment
- Primary Purpose: Other
- Masking: Double (Participant, Care Provider)
- Study Primary Completion Date: December 2025
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.
- Drug: Tocotrienol (TCT)
- TCT is a natural vitamin E supplement with a long history of safe dietary consumption in humans. The objective of the current trial is to validate the outcome observed in an earlier trial that oral TCT attenuates the rise in MELD score over time in patients with end stage liver disease/cirrhosis.
- Other: Placebo
- Control study capsule that includes no study product (Vitamin E – Tocotrienol)
Arms, Groups and Cohorts
- Placebo Comparator: Placebo Vehicle
- Subjects will take 2 placebo capsules following AM meal, 2 placebo capsules following PM capsules
- Active Comparator: Tocotrienol supplement
- Subjects will take (2) 200 mg TCT capsules following AM meal, (2) 200 mg TCT following PM meal
Clinical Trial Outcome Measures
- Effect of Oral tocotrienols (TCT) on Model for End-Stage Liver Disease (MELD) score.
- Time Frame: 3 years
- Lab tests to calculate MELD score will be taken at baseline study visit and the last study visit ( Study visit 8 – 3 years) to see if Oral TCT will significantly attenuate the rise in MELD score over time in patients with End Stage Liver Disease / Cirrhosis
Participating in This Clinical Trial
- 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
- 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
- Lead Sponsor
- Indiana University
- Malaysia Palm Oil Board
- Provider of Information About this Clinical Study
- Principal Investigator: Raj Vuppalanchi, Professor – Indiana University
- Overall Official(s)
- Chandan K Sen, Ph.D, Study Chair, Indiana University School of Medicine
- Raj Vuppalanchi, M.D., Principal Investigator, Indiana Unviersity School of Medicine
- Overall Contact(s)
- Jennifer Mohnacky, RN, 317-278-2715, firstname.lastname@example.org
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