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Vitamin E Dosing Study (VEDS)

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ClinicalTrials.gov Identifier: NCT04801849
Recruitment Status : Not yet recruiting
First Posted : March 17, 2021
Last Update Posted : April 27, 2021
Sponsor:
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary:
This is a multicenter, randomized, double masked, placebo-controlled, parallel treatment groups dosing trial of Vitamin E in adult nonalcoholic fatty liver disease (NAFLD).

Condition or disease Intervention/treatment Phase
Nonalcoholic Fatty Liver Disease Nonalcoholic Steatohepatitis Drug: d-alpha-tocopherol Drug: Placebo Phase 2

Detailed Description:
Adults age 18 years or older will be enrolled for 48 weeks and treated with 200 international units (IU), 400 IU, or 800 IU of Vitamin E or matching placebo for 24 weeks. The primary objective of the study is to determine the minimum effective dose of Vitamin E (d-alpha-tocopherol) based upon relative change in alanine aminotransferase (ALT) from baseline to 24 weeks.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: multicenter, randomized, double masked, placebo-controlled, parallel treatment groups
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Vitamin E Dosing Study (VEDS): A Dose Finding Study of Vitamin E for the Treatment of Adult NAFLD
Estimated Study Start Date : August 2021
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : February 2024


Arm Intervention/treatment
Active Comparator: Vitamin E, 200 IU
200 IU of d-alpha tocopherol (vitamin E) taken once daily with breakfast
Drug: d-alpha-tocopherol
Participants will be assigned to take 200 IU, 400 IU, or 800 IU of vitamin E in matching capsules daily for 24 weeks
Other Name: vitamin E

Active Comparator: Vitamin E, 400 IU
400 IU of d-alpha tocopherol (vitamin E) taken once daily with breakfast
Drug: d-alpha-tocopherol
Participants will be assigned to take 200 IU, 400 IU, or 800 IU of vitamin E in matching capsules daily for 24 weeks
Other Name: vitamin E

Active Comparator: Vitamin E, 800 IU
800 IU of d-alpha tocopherol (vitamin E) taken once daily with breakfast
Drug: d-alpha-tocopherol
Participants will be assigned to take 200 IU, 400 IU, or 800 IU of vitamin E in matching capsules daily for 24 weeks
Other Name: vitamin E

Placebo Comparator: Placebo
matching placebo taken once daily with breakfast
Drug: Placebo
Participants will take a placebo vitamin E capsule daily for 24 weeks




Primary Outcome Measures :
  1. Relative change in alanine aminotransferase (ALT) from baseline to 24 weeks [ Time Frame: 24 weeks ]
    ALT value in units/liter (U/L)


Secondary Outcome Measures :
  1. Proportion of patients achieving normalization of alanine aminotransferase (ALT) at 24 weeks [ Time Frame: 24 weeks ]
    Normalization of ALT (U/L) is defined as a decrease in ALT to less than or equal to the ULN at the 24 week visit among participants who had an ALT value greater than ULN at baseline. Values for upper limits of normal (ULN) are defined at each clinical center per institutional guidelines.

  2. Mean change in serum alanine aminotransferase (ALT) from baseline [ Time Frame: 24 weeks ]
    ALT value in U/L

  3. Mean change in serum aspartate aminotransferase (AST) from baseline [ Time Frame: 24 weeks ]
    AST value in U/L

  4. Mean change in hepatic steatosis (fat in the liver) score determined by Fibroscan® Controlled Attenuation Parameter (CAP) software function [ Time Frame: 24 weeks ]

    CAP (Control Attenuation Parameter) is expressed in decibels per meter (dB/m). This value is the median of all valid measurements performed during the examination. It ranges from 100 to 400 dB/m. Higher dB/m indicates worse liver fat.

    238 to 260 dB/m: 11% to 33% of liver with fatty change; 260 to 290 dB/m: 34% to 66% of liver with fatty change; 290 to 400 dB/m: at least 67% of liver with fatty change


  5. Mean change in liver stiffness from baseline assessed by Fibroscan® [ Time Frame: 24 weeks ]
    Fibroscan® measures stiffness in kiloPascal's (kPa) and ranges from 2 to 75. Normal range of FibroScan is between 2 to 7 kPa, and the average normal result is 5.3kPa. Higher kPa means more stiffness (scarring).



Information from the National Library of Medicine

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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:

  • 18 years of age or older as of the initial screening interview and provision of consent
  • Histologic evidence of NAFLD based upon a liver biopsy obtained no more than 3 years prior to randomization and a NAFLD activity score (NAS) of 3 or more
  • ALT ≥ 60 U/L at randomization (within 30 days)

Exclusion Criteria:

  • Concurrent or prior use (within 90 days) of vitamin E supplements in excess of 40 IU/day
  • Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening (significant alcohol consumption is defined as more than 20 g/day (> 14 drinks per week) in females and more than 30 g/day (>21 drinks per week) in males, on average)
  • Inability to reliably quantify alcohol consumption based upon local study physician judgment
  • Continued use of drugs historically associated with NAFLD (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, and other known hepatotoxins) for more than 2 weeks in the 6 months prior to randomization
  • Current use of chronic anticoagulation therapy (not including aspirin)
  • Platelet count below 100,000 /mm3 within 90 days of enrollment
  • History of condition(s) that cause increased risk of bleeding, including hemophilia A, hemophilia B, von Willebrand disease, or other clotting factor deficiencies.
  • Prior or planned (during the study period) bariatric surgery (eg, gastroplasty, roux-en-Y gastric bypass)
  • Uncontrolled diabetes defined as HbA1c 9.5% or higher within 60 days prior to enrollment
  • Clinical evidence of hepatic decompensation as defined by the presence of any of the following abnormalities:
  • Serum albumin less than 3.2 grams per dL
  • International Normalized Ratio (INR) greater than 1.3
  • Direct bilirubin greater than 1.0 milligrams per dL
  • History of esophageal varices, ascites or hepatic encephalopathy
  • Evidence of other forms of chronic liver disease:
  • Hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg)
  • Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA
  • Evidence of ongoing autoimmune liver disease as defined by compatible liver histology
  • Primary biliary cirrhosis as defined by the presence of at least 2 of these criteria Biochemical evidence of cholestasis based mainly on alkaline phosphatase elevation Presence of anti-mitochondrial antibody (AMA) Histologic evidence of nonsuppurative destructive cholangitis and destruction of interlobular bile ducts
  • Primary sclerosing cholangitis
  • Known history of Wilson disease, alpha-1-antitrypsin liver disease or hemochromatosis Any other type of liver disease that is currently active other than nonalcoholic steatohepatitis (NASH) such as drug-induced liver disease, liver cancer or bile duct obstruction.
  • Serum alanine aminotransferase (ALT) greater than 400 U/L within 90 days of enrollment
  • Serum creatinine of 2.0 milligrams per dL or greater
  • History of biliary diversion
  • Known positivity for Human Immunodeficiency Virus (HIV) infection
  • Active, serious medical disease with likely life expectancy less than 5 years
  • Active substance abuse including inhaled or injection drugs in the year prior to screening
  • Pregnancy, planned pregnancy, potential for pregnancy and unwillingness to use effective birth control during the trial, breast feeding
  • Participation in an Investigational New Drug (IND) trial in the 30 days before randomization
  • Any other condition which, in the opinion of the investigator, would impede compliance or hinder completion of the study, including inability to swallow treatment capsules
  • Failure or inability to give informed consent

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): NCT04801849


Contacts
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Contact: Emily Sharkey, MS, MBA 410-955-8183 esharke5@jhu.edu
Contact: Laura Miriel, BS lmiriel1@jhu.edu

Locations
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United States, California
University of California, San Diego
La Jolla, California, United States, 92103
Contact: Egbert Madamba    858-246-1394    emadamba@ucsd.edu   
Contact: Lisa Richards       lrichards@ucsd.edu   
Principal Investigator: Rohit Loomba, MD         
University of Southern California
Los Angeles, California, United States, 90089
Contact: Christy Rico    323-442-1100    christy.rico@med.usc.edu   
Contact: Daisy Olvera    (323) 442-0535    daisy.olvera@med.usc.edu   
Principal Investigator: Norah Terrault, MD, MPH         
University of California, San Francisco
San Francisco, California, United States, 94143
Contact: Rae Davis    415-514-3274    rayshawnda.davis@ucsf.edu   
Contact: Remi Awe    (415) 502-2906    remilekun.awe@ucsf.edu   
Principal Investigator: Norah Terrault, MD         
Sub-Investigator: Bilal Hameed, MD         
United States, Indiana
Indiana University- Adults
Indianapolis, Indiana, United States, 46202
United States, Missouri
St. Louis University
Saint Louis, Missouri, United States, 63110
Contact: Theresa Cattoor, RN    314-977-9355    theresa.cattooor@health.slu.edu   
Contact: Shirley Campbell    (314) 977-9336    shirley.campbell@health.slu.edu   
Principal Investigator: Brent Tetri, MD         
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Contact: Mariko Kopping    919-684-4798    mariko.kopping@duke.edu   
Contact: Stephanie Buie    (919) 684-4138    stephanie.buie@duke.edu   
Principal Investigator: Anna Mae Diehl, MD         
Sub-Investigator: Manal Abdelmalek, MD         
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Contact: Alina Tuladhar    216-445-0688    tuladha@ccf.org   
Contact: Annette Bellar    (216) 636-5247    bellara@ccf.org   
Principal Investigator: Srinivasan Dasarathy, MD         
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Contact: Sherry Boyett    804-828-5434    slboyett@vcu.edu   
Contact: Jolene Schlosser    (804) 828-9195    jschlosser@vcu.edu   
Principal Investigator: Arun J Sanyal, MD         
United States, Washington
Liver Institute Northwest
Seattle, Washington, United States, 98105
Contact: Tommy Clark    206-536-3030    tclark@liverinstitutenw.org   
Contact: Heather Harris    (206) 536-3030    hharris@liverinstitutenw.org   
Principal Investigator: Kris Kowdley, MD         
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Arun Sanyal, MD Virginia Commonwealth University
Additional Information:
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Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT04801849    
Other Study ID Numbers: 10 VEDS
U24DK061730 ( U.S. NIH Grant/Contract )
U01DK061732 ( U.S. NIH Grant/Contract )
U01DK061713 ( U.S. NIH Grant/Contract )
U01DK061737 ( U.S. NIH Grant/Contract )
U01DK061728 ( U.S. NIH Grant/Contract )
U01DK061718 ( U.S. NIH Grant/Contract )
U01DK061734 ( U.S. NIH Grant/Contract )
U01DK061738 ( U.S. NIH Grant/Contract )
U01DK061731 ( U.S. NIH Grant/Contract )
First Posted: March 17, 2021    Key Record Dates
Last Update Posted: April 27, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: This study will comply with the NIH Data Sharing Policy and Results information from this trial will be submitted to ClinicalTrials.gov and a public use database deposited with the NIDDK Central Repository.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Analytic Code
Time Frame: Data from this study may be requested from the NIDDK Central Repository (https://www.niddkrepository.org/search/study/) two years after the completion of the primary outcome.
Access Criteria: Apply through the NIDDK Central Repository:
URL: http://repository.niddk.nih.gov/home/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Vitamin E
Nonalcoholic Fatty Liver Disease
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Vitamin E
Tocopherols
Tocotrienols
alpha-Tocopherol
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents