Tocotrienol Against the Progression of End Stage Liver Disease

July 19, 2023 updated by: Raj Vuppalanchi, Indiana University
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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

70

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Kaitlyn Depinet, FNP-C
  • Phone Number: 3172782747
  • Email: kdepinet@iu.edu

Study Contact Backup

  • Name: Sashwati Roy, Ph.D
  • Phone Number: 3172782706
  • Email: roysa@iu.edu

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 17 with <25% change in MELD over the past 60 days prior to enrollment (*Total number of patients with MELD of 8-9 or MELD of 16-17 cannot exceed 40% of cohort)
  • 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:

  1. Rapid deterioration of liver function, as defined by an increase in MELD score ≥25% over the past 60 days prior to enrollment
  2. Hepatocellular carcinoma
  3. Positive HIV/AIDS, or other chronic immunodeficiency
  4. Concurrent hepatitis B or C infection
  5. Current drug and/or alcohol abuse (per treating physician)
  6. Bacterial infection at time of enrollment
  7. Daily use of dedicated vitamin E supplementation (greater than 100 IU per day) within the 3 months prior to study participation
  8. Platelets <35,000 cells/µL, neutrophils <1000 cells/µL, hemoglobin <10g/dL, total bilirubin >3mg/dL, serum creatinine >2.0mg/dL
  9. Women who are pregnant, breastfeeding, or plan to become pregnant during course of study participation (36 months)
  10. Other significant comorbidities which limit the subject's life expectancy to less than 36 months
  11. Concurrent enrollment in another interventional clinical trial
  12. ALT >250 U/L
  13. AST > 250 U/L
  14. Hemoglobin A1C ≥ 9.5 %
  15. History of liver transplantation
  16. Current or history of HCC
  17. Any weight reduction surgery in the preceding 2 years prior to screening or planned surgery during the study
  18. Malignancy within 5 years of screening with the exception of a Adequately treated carcinoma in situ of the cervix b. Adequately treated basal or squamous cell cancer or other localized non-melanoma skin cancer

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo Vehicle
Subjects will take 2 placebo capsules following AM meal, 2 placebo capsules following PM capsules
Other: Placebo
Control study capsule that includes no study product (Vitamin E - Tocotrienol)
Other Names:
  • vehicle
Active Comparator: Tocotrienol supplement
Subjects will take (2) 200 mg TCT capsules following AM meal, (2) 200 mg TCT 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 17 - 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
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Child-Pugh Score
Time Frame: 3 years
change in Child-Pugh Score
3 years
Change in ALT Alanine transaminase
Time Frame: 3 years
Change in ALT (Alanine transaminase)
3 years
Events of hepatic decompensation
Time Frame: 3 yrs
Events of hepatic decompensation
3 yrs
New onset ascites requiring treatment with or without paracentesis
Time Frame: 3 yrs
New onset ascites requiring treatment with or without paracentesis
3 yrs
GI bleed attributed to variceal bleeding
Time Frame: 3 yrs
GI bleed attributed to variceal bleeding, requires evaluation by an endoscopy
3 yrs
Hepatic encephalopathy requiring treatment
Time Frame: 3 yrs
Hepatic encephalopathy requiring treatment, Grade 2 or above according to West Haven Criteria
3 yrs
Need for Liver transplant
Time Frame: 3 yrs
Need for liver transplant
3 yrs
Death
Time Frame: 3 yrs
did death occur
3 yrs
Liver fibrosis
Time Frame: 3 yrs
Liver fibrosis as measured by change in LSM by vibration-controlled transient elastography
3 yrs
Adverse events
Time Frame: 3 yrs
Did any AEs occur
3 yrs

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Indiana University

Collaborators

Malaysia Palm Oil Board

Investigators

  • Study Chair: Chandan K Sen, Ph.D, Indiana University School of Medicine
  • Principal Investigator: Raj Vuppalanchi, M.D., Indiana Unviersity School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2019

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

June 26, 2015

First Submitted That Met QC Criteria

October 16, 2015

First Posted (Estimated)

October 20, 2015

Study Record Updates

Last Update Posted (Actual)

July 20, 2023

Last Update Submitted That Met QC Criteria

July 19, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1807361301

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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