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Vitamin E Dosing Study (VEDS)

Primary Purpose

Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Vitamin E
Placebo
Sponsored by
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nonalcoholic Fatty Liver Disease focused on measuring Vitamin E, Nonalcoholic Fatty Liver Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 18 years of age or older as of the initial screening interview and provision of consent
  • FibroScan CAP>280 dB/m within 60 days prior to randomization.
  • ALT ≥ 60 U/L within 30 days of randomization

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 (~1.5 drinks/day) (> 10.5 drinks per week) in females and more than 30 g/day (~2 drinks/day) (>14 drinks per week) in males, respectively. One "standard" drink (or one alcoholic drink equivalent) contains roughly 14 grams of pure alcohol, which is found in: 12 ounces of regular beer, 5 ounces of wine, or 1.5 ounces of distilled spirits).
  • 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 anticoagulation therapy (not including antiplatelet agents such as aspirin or clopidogrel)
  • Platelet count below 150,000 /mm3 within 90 days of randomization
  • 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 randomization
  • Clinical evidence of hepatic decompensation as defined by the presence of any of the following abnormalities:

    • Serum albumin less than 3.2 g/dL
    • International Normalized Ratio (INR) greater than 1.3
    • Direct bilirubin greater than 1.0 mg/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 (i) Biochemical evidence of cholestasis based mainly on alkaline phosphatase elevation (ii) Presence of anti-mitochondrial antibody (AMA) (iii) Histologic evidence of nonsuppurative destructive cholangitis and destruction of interlobular bile ducts[1]
    • 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 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 randomization
  • Moderate or severe renal impairment (serum creatinine ≥ 2.0 mg/dL or eGFR < 60 mg/mL/1.73m2)
  • History of biliary diversion or evidence of current biliary obstruction
  • 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 ≥ 1 effective form(s) of birth control during the trial, breast feeding
  • Current use of medications that may impact the absorption of fat-soluble vitamins (i.e. orlistat or cholestyramine)
  • Pre-existing history of fat malabsorption
  • Males at high risk of prostate cancer, including:

    • PSA >ULN at baseline
    • History of prostate cancer
    • Age 45 or older with a first-degree relative (father or brother) diagnosed with prostate cancer at an early age (younger than age 65).
    • Age 40 or older with more than one first-degree relative who had prostate cancer at an early age (younger than age 65)
  • Participation in an 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

Sites / Locations

  • University of California, San DiegoRecruiting
  • University of Southern CaliforniaRecruiting
  • University of California, San FranciscoRecruiting
  • Indiana University- AdultsRecruiting
  • St. Louis University
  • Duke University Medical CenterRecruiting
  • Cleveland Clinic FoundationRecruiting
  • Virginia Commonwealth UniversityRecruiting
  • Liver Institute NorthwestRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

Vitamin E, 200 IU

Vitamin E, 400 IU

Vitamin E, 800 IU

Placebo

Arm Description

200 IU of d-alpha tocopherol (vitamin E) taken once daily with breakfast

400 IU of d-alpha tocopherol (vitamin E) taken once daily with breakfast

800 IU of d-alpha tocopherol (vitamin E) taken once daily with breakfast

matching placebo taken once daily with breakfast

Outcomes

Primary Outcome Measures

Relative change in alanine aminotransferase (ALT) from baseline to 24 weeks
ALT value in units/liter (U/L)

Secondary Outcome Measures

Proportion of patients achieving normalization of alanine aminotransferase (ALT) at 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.
Mean change in serum alanine aminotransferase (ALT) from baseline
ALT value in U/L
Mean change in serum aspartate aminotransferase (AST) from baseline
AST value in U/L
Mean change in hepatic steatosis (fat in the liver) score determined by Fibroscan® Controlled Attenuation Parameter (CAP) software function
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
Mean change in liver stiffness from baseline assessed by Fibroscan®
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).

Full Information

First Posted
March 12, 2021
Last Updated
April 27, 2023
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators
Duke University, Liver Institute Northwest, Indiana University, St. Louis University, University of California, San Diego, University of Southern California, University of California, San Francisco, Virginia Commonwealth University, Case Western Reserve University
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1. Study Identification

Unique Protocol Identification Number
NCT04801849
Brief Title
Vitamin E Dosing Study
Acronym
VEDS
Official Title
Vitamin E Dosing Study (VEDS): A Dose Finding Study of Vitamin E for the Treatment of Adult NAFLD
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 5, 2022 (Actual)
Primary Completion Date
August 30, 2024 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators
Duke University, Liver Institute Northwest, Indiana University, St. Louis University, University of California, San Diego, University of Southern California, University of California, San Francisco, Virginia Commonwealth University, Case Western Reserve University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis
Keywords
Vitamin E, Nonalcoholic Fatty Liver Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
multicenter, randomized, double masked, placebo-controlled, parallel treatment groups
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Vitamin E, 200 IU
Arm Type
Active Comparator
Arm Description
200 IU of d-alpha tocopherol (vitamin E) taken once daily with breakfast
Arm Title
Vitamin E, 400 IU
Arm Type
Active Comparator
Arm Description
400 IU of d-alpha tocopherol (vitamin E) taken once daily with breakfast
Arm Title
Vitamin E, 800 IU
Arm Type
Active Comparator
Arm Description
800 IU of d-alpha tocopherol (vitamin E) taken once daily with breakfast
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
matching placebo taken once daily with breakfast
Intervention Type
Drug
Intervention Name(s)
Vitamin E
Other Intervention Name(s)
d-alpha-tocopherol
Intervention Description
Participants will be assigned to take 200 IU, 400 IU, or 800 IU of vitamin E in matching capsules daily for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will take a placebo vitamin E capsule daily for 24 weeks
Primary Outcome Measure Information:
Title
Relative change in alanine aminotransferase (ALT) from baseline to 24 weeks
Description
ALT value in units/liter (U/L)
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Proportion of patients achieving normalization of alanine aminotransferase (ALT) at 24 weeks
Description
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.
Time Frame
24 weeks
Title
Mean change in serum alanine aminotransferase (ALT) from baseline
Description
ALT value in U/L
Time Frame
24 weeks
Title
Mean change in serum aspartate aminotransferase (AST) from baseline
Description
AST value in U/L
Time Frame
24 weeks
Title
Mean change in hepatic steatosis (fat in the liver) score determined by Fibroscan® Controlled Attenuation Parameter (CAP) software function
Description
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
Time Frame
24 weeks
Title
Mean change in liver stiffness from baseline assessed by Fibroscan®
Description
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).
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 18 years of age or older as of the initial screening interview and provision of consent FibroScan CAP>280 dB/m within 60 days prior to randomization. ALT ≥ 60 U/L within 30 days of randomization 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 (~1.5 drinks/day) (> 10.5 drinks per week) in females and more than 30 g/day (~2 drinks/day) (>14 drinks per week) in males, respectively. One "standard" drink (or one alcoholic drink equivalent) contains roughly 14 grams of pure alcohol, which is found in: 12 ounces of regular beer, 5 ounces of wine, or 1.5 ounces of distilled spirits). 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 anticoagulation therapy (not including antiplatelet agents such as aspirin or clopidogrel) Platelet count below 150,000 /mm3 within 90 days of randomization 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 randomization Clinical evidence of hepatic decompensation as defined by the presence of any of the following abnormalities: Serum albumin less than 3.2 g/dL International Normalized Ratio (INR) greater than 1.3 Direct bilirubin greater than 1.0 mg/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 (i) Biochemical evidence of cholestasis based mainly on alkaline phosphatase elevation (ii) Presence of anti-mitochondrial antibody (AMA) (iii) Histologic evidence of nonsuppurative destructive cholangitis and destruction of interlobular bile ducts[1] 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 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 randomization Moderate or severe renal impairment (serum creatinine ≥ 2.0 mg/dL or eGFR < 60 mg/mL/1.73m2) History of biliary diversion or evidence of current biliary obstruction 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 ≥ 1 effective form(s) of birth control during the trial, breast feeding Current use of medications that may impact the absorption of fat-soluble vitamins (i.e. orlistat or cholestyramine) Pre-existing history of fat malabsorption Males at high risk of prostate cancer, including: PSA >ULN at baseline History of prostate cancer Age 45 or older with a first-degree relative (father or brother) diagnosed with prostate cancer at an early age (younger than age 65). Age 40 or older with more than one first-degree relative who had prostate cancer at an early age (younger than age 65) Participation in an 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Emily Sharkey, MS, MBA
Phone
410-955-8183
Email
esharke5@jhu.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Laura Miriel, BS
Email
lmiriel1@jhu.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arun Sanyal, MD
Organizational Affiliation
Virginia Commonwealth University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92103
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Egbert Madamba
Phone
858-246-1394
Email
emadamba@ucsd.edu
First Name & Middle Initial & Last Name & Degree
Lisa Richards
Email
lrichards@ucsd.edu
First Name & Middle Initial & Last Name & Degree
Rohit Loomba, MD
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90089
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christy Rico
Phone
323-442-1100
Email
christy.rico@med.usc.edu
First Name & Middle Initial & Last Name & Degree
Daisy Olvera
Phone
(323) 442-0535
Email
daisy.olvera@med.usc.edu
First Name & Middle Initial & Last Name & Degree
Norah Terrault, MD, MPH
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rae Davis
Phone
415-514-3274
Email
rayshawnda.davis@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Remi Awe
Phone
(415) 502-2906
Email
remilekun.awe@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Norah Terrault, MD
First Name & Middle Initial & Last Name & Degree
Bilal Hameed, MD
Facility Name
Indiana University- Adults
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa Garrison, BSN
Phone
317-278-3206
Email
ljgarris@iu.edu
First Name & Middle Initial & Last Name & Degree
Regina Webster
Phone
(317) 278-3584
Email
reginaw@iu.edu
First Name & Middle Initial & Last Name & Degree
Naga Chalasani, MD
Facility Name
St. Louis University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Theresa Cattoor, RN
Phone
314-977-9355
Email
theresa.cattooor@health.slu.edu
First Name & Middle Initial & Last Name & Degree
Shirley Campbell
Phone
(314) 977-9336
Email
shirley.campbell@health.slu.edu
First Name & Middle Initial & Last Name & Degree
Brent Tetri, MD
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariko Kopping
Phone
919-684-4798
Email
mariko.kopping@duke.edu
First Name & Middle Initial & Last Name & Degree
Dawn Piercy
Phone
(919) 684-0129
Email
dawn.piercy@duke.edu
First Name & Middle Initial & Last Name & Degree
Anna Mae Diehl, MD
First Name & Middle Initial & Last Name & Degree
Manal Abdelmalek, MD
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rahul Yerrapothu
Phone
216-445-4863
Email
yerrapr@ccf.org
First Name & Middle Initial & Last Name & Degree
Annette Bellar
Phone
(216) 636-5247
Email
bellara@ccf.org
First Name & Middle Initial & Last Name & Degree
Srinivasan Dasarathy, MD
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sherry Boyett
Phone
804-828-5434
Email
slboyett@vcu.edu
First Name & Middle Initial & Last Name & Degree
Arun J Sanyal, MD
Facility Name
Liver Institute Northwest
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew Buysse
Phone
206-536-3030
Email
abuysse@liverinstitutenw.org
First Name & Middle Initial & Last Name & Degree
Pannapat Angkanaworakul
Phone
(206) 536-3030
Email
pannapat@liverinstitutenw.org
First Name & Middle Initial & Last Name & Degree
Kris Kowdley, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing Access Criteria
Apply through the NIDDK Central Repository:
IPD Sharing URL
http://repository.niddk.nih.gov/home/
Links:
URL
http://jhuccs1.us/nash/open/centers/centers.htm
Description
Nonalcoholic Steatohepatitis Clinical Research Network Centers
URL
http://www2.niddk.nih.gov/
Description
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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Vitamin E Dosing Study

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