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Liver Trial on Oral Tocotrienol

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ClinicalTrials.gov Identifier: NCT02581085
Recruitment Status : Recruiting
First Posted : October 20, 2015
Last Update Posted : March 22, 2018
Sponsor:
Collaborator:
Malaysia Palm Oil Board
Information provided by (Responsible Party):
Chandan K Sen, Ohio State University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
End Stage Liver Disease Hepatitis C Dietary Supplement: Tocotrienol Other: Placebo Phase 1 Phase 2

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


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Other
Official Title: Tocotrienol Against the Progression of End Stage Liver Disease
Study Start Date : February 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021


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 Name: vehicle

Active Comparator: Tocotrienol supplement
Subjects will take (2) 200 mg TCT capsules following AM meal, (2) 200 mg TCT following PM meal
Dietary Supplement: 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 Name: Vitamin E




Primary Outcome Measures :
  1. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02581085


Contacts
Contact: David Paoletto, RN 614-685-3173 David.Paoletto@osumc.edu
Contact: Sashwati Roy, Ph.D 614-247-7657 sashwati.roy@osumc.edu

Locations
United States, Ohio
University Hospital East Recruiting
Columbus, Ohio, United States, 43205
Contact: David Paoletto, RN    614-685-3173    David.Paoletto@osumc.edu   
Contact: Amy Hoover, LPN    614-366-2783    Amy.Hoover@osumc.edu   
Martha Morehouse Medical Plaza Recruiting
Columbus, Ohio, United States, 43210
Contact: David Paoletto, RN    614-685-3173    david.paoletto@osumc.edu   
Contact: Elizabeth Murphy, BS    614-685-3173    elizabeth.murphy@osumc.edu   
The Ohio State Unversity Hospital Recruiting
Columbus, Ohio, United States, 43210
Contact: David Paoletto, RN    614-685-3173    David.Paoletto@osumc.edu   
Contact: Sashwati Roy, PhD    614-247-7657    sashwati.roy@osumc.edu   
Sponsors and Collaborators
Ohio State University
Malaysia Palm Oil Board
Investigators
Principal Investigator: Chandan K Sen, Ph.D The Ohio State University Wexner Medical Center

Publications:
Responsible Party: Chandan K Sen, Professor, Ohio State University
ClinicalTrials.gov Identifier: NCT02581085     History of Changes
Other Study ID Numbers: 2015H0112
First Posted: October 20, 2015    Key Record Dates
Last Update Posted: March 22, 2018
Last Verified: March 2018

Keywords provided by Chandan K Sen, Ohio State University:
Tocotrienol
Vitamin E

Additional relevant MeSH terms:
Hepatitis C
Liver Diseases
End Stage Liver Disease
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hepatitis
Digestive System Diseases
Liver Failure
Hepatic Insufficiency
Vitamins
Vitamin E
Tocopherols
Tocotrienols
alpha-Tocopherol
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents