Tocotrienol Against the Progression of End Stage Liver Disease
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| ClinicalTrials.gov Identifier: NCT02581085 |
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Recruitment Status :
Recruiting
First Posted : October 20, 2015
Last Update Posted : February 8, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| End Stage Liver Disease NASH - Nonalcoholic Steatohepatitis NAFLD - Nonalcoholic Fatty Liver Disease | Drug: Tocotrienol (TCT) Other: Placebo | Phase 2 |
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 (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 |
| Actual Study Start Date : | November 1, 2019 |
| Estimated Primary Completion Date : | December 31, 2027 |
| Estimated Study Completion Date : | December 31, 2028 |
| Arm | Intervention/treatment |
|---|---|
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Placebo Comparator: Placebo Vehicle
Subjects will take 2 placebo capsules following AM meal, 2 placebo capsules following PM capsules
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Other: Placebo
Control study capsule that includes no study product (Vitamin E - Tocotrienol)
Other Name: vehicle |
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Active Comparator: Tocotrienol supplement
Subjects will take (2) 200 mg TCT capsules following AM meal, (2) 200 mg TCT following PM meal
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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. |
- 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
- Change in Child-Pugh Score [ Time Frame: 3 years ]change in Child-Pugh Score
- Change in ALT Alanine transaminase [ Time Frame: 3 years ]Change in ALT (Alanine transaminase)
- Events of hepatic decompensation [ Time Frame: 3 yrs ]Events of hepatic decompensation
- New onset ascites requiring treatment with or without paracentesis [ Time Frame: 3 yrs ]New onset ascites requiring treatment with or without paracentesis
- GI bleed attributed to variceal bleeding [ Time Frame: 3 yrs ]GI bleed attributed to variceal bleeding, requires evaluation by an endoscopy
- Hepatic encephalopathy requiring treatment [ Time Frame: 3 yrs ]Hepatic encephalopathy requiring treatment, Grade 2 or above according to West Haven Criteria
- Need for Liver transplant [ Time Frame: 3 yrs ]Need for liver transplant
- Death [ Time Frame: 3 yrs ]did death occur
- Liver fibrosis [ Time Frame: 3 yrs ]Liver fibrosis as measured by change in LSM by vibration-controlled transient elastography
- Adverse events [ Time Frame: 3 yrs ]Did any AEs occur
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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:
- Rapid deterioration of liver function, as defined by an increase in MELD score ≥25% over the past 60 days prior to enrollment
- Hepatocellular carcinoma
- Positive HIV/AIDS, or other chronic immunodeficiency
- Concurrent hepatitis B or C infection
- Current drug and/or alcohol abuse (per treating physician)
- Bacterial infection at time of enrollment
- Daily use of dedicated vitamin E supplementation (greater than 100 IU per day) within the 3 months prior to study participation
- Platelets <35,000 cells/µL, neutrophils <1000 cells/µL, hemoglobin <10g/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
- Concurrent enrollment in another interventional clinical trial
- ALT >250 U/L
- AST > 250 U/L
- Hemoglobin A1C ≥ 9.5 %
- History of liver transplantation
- Current or history of HCC
- Any weight reduction surgery in the preceding 2 years prior to screening or planned surgery during the study
- 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
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
| Contact: Amy Miller | 317-278-2720 | amym@iu.edu | |
| Contact: Sashwati Roy, Ph.D | 3172782706 | roysa@iu.edu |
| United States, Indiana | |
| IU Health Unviersity Hospital | Recruiting |
| Indianapolis, Indiana, United States, 46202 | |
| Contact: Heather Adams, RN 317-962-1130 hejadams@iu.edu | |
| Contact: Anna Smith, RN asmith81@iuhealth.org | |
| Study Chair: | Chandan K Sen, Ph.D | Indiana University School of Medicine | |
| Principal Investigator: | Raj Vuppalanchi, M.D. | Indiana Unviersity School of Medicine |
| Responsible Party: | Raj Vuppalanchi, Professor, Indiana University |
| ClinicalTrials.gov Identifier: | NCT02581085 |
| Other Study ID Numbers: |
1807361301 |
| First Posted: | October 20, 2015 Key Record Dates |
| Last Update Posted: | February 8, 2023 |
| Last Verified: | February 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Tocotrienol Vitamin E |
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Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease End Stage Liver Disease Digestive System Diseases Liver Failure Hepatic Insufficiency Tocotrienols |
Vitamin E Tocopherols Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Physiological Effects of Drugs Vitamins Micronutrients |