Vitamin E Dosing Study

NCT ID: NCT04801849

Last Updated: 2025-09-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-05

Study Completion Date

2025-06-30

Brief Summary

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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

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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.

Conditions

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Nonalcoholic Fatty Liver Disease Nonalcoholic Steatohepatitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

multicenter, randomized, double masked, placebo-controlled, parallel treatment groups
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Vitamin E, 200 IU

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

Group Type ACTIVE_COMPARATOR

Vitamin E

Intervention Type DRUG

Participants will be assigned to take 200 IU, 400 IU, or 800 IU of vitamin E in matching capsules daily for 24 weeks

Vitamin E, 400 IU

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

Group Type ACTIVE_COMPARATOR

Vitamin E

Intervention Type DRUG

Participants will be assigned to take 200 IU, 400 IU, or 800 IU of vitamin E in matching capsules daily for 24 weeks

Vitamin E, 800 IU

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

Group Type ACTIVE_COMPARATOR

Vitamin E

Intervention Type DRUG

Participants will be assigned to take 200 IU, 400 IU, or 800 IU of vitamin E in matching capsules daily for 24 weeks

Placebo

matching placebo taken once daily with breakfast

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Participants will take a placebo vitamin E capsule daily for 24 weeks

Interventions

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Vitamin E

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

Placebo

Participants will take a placebo vitamin E capsule daily for 24 weeks

Intervention Type DRUG

Other Intervention Names

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d-alpha-tocopherol

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Duke University

OTHER

Sponsor Role collaborator

Liver Institute Northwest

UNKNOWN

Sponsor Role collaborator

Indiana University

OTHER

Sponsor Role collaborator

St. Louis University

OTHER

Sponsor Role collaborator

University of California, San Diego

OTHER

Sponsor Role collaborator

University of Southern California

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role collaborator

Virginia Commonwealth University

OTHER

Sponsor Role collaborator

The Cleveland Clinic

OTHER

Sponsor Role collaborator

Johns Hopkins Bloomberg School of Public Health

OTHER

Sponsor Role collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Arun Sanyal, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

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University of California, San Diego

La Jolla, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Indiana University- Adults

Indianapolis, Indiana, United States

Site Status

St. Louis University

St Louis, Missouri, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Liver Institute Northwest

Seattle, Washington, United States

Site Status

Countries

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United States

Related Links

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http://jhuccs1.us/nash/open/centers/centers.htm

Nonalcoholic Steatohepatitis Clinical Research Network Centers

http://www2.niddk.nih.gov/

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Other Identifiers

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U24DK061730

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061732

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061713

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061737

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061728

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061718

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061734

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061738

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061731

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00240822

Identifier Type: OTHER

Identifier Source: secondary_id

10 VEDS

Identifier Type: -

Identifier Source: org_study_id

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