Clinical trial NCT04801849: Vitamin E Dosing Study
Official title: Vitamin E Dosing Study (VEDS): A Dose Finding Study of Vitamin E for the Treatment of Adult NAFLD
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Nonalcoholic Fatty Liver Disease
Nonalcoholic Steatohepatitis
Keywords: Vitamin E
Nonalcoholic Fatty Liver Disease
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
Collaborators: name: Duke University
name: Liver Institute Northwest
name: Indiana University
name: St. Louis University
name: University of California, San Diego
name: University of Southern California
name: University of California, San Francisco
name: Virginia Commonwealth University
name: The Cleveland Clinic
name: Johns Hopkins Bloomberg School of Public Health
First posted: 2021-03-17
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multicenter, randomized, double masked, placebo-controlled, parallel treatment groups
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Relative change in alanine aminotransferase (ALT) from baseline to 24 weeks
timeFrame: 24 weeks
Secondary outcomes:
measure: Proportion of patients achieving normalization of alanine aminotransferase (ALT) at 24 weeks
timeFrame: 24 weeks
measure: Mean change in serum alanine aminotransferase (ALT) from baseline
timeFrame: 24 weeks
measure: Mean change in serum aspartate aminotransferase (AST) from baseline
timeFrame: 24 weeks
measure: Mean change in hepatic steatosis (fat in the liver) score determined by Fibroscan® Controlled Attenuation Parameter (CAP) software function
timeFrame: 24 weeks
measure: Mean change in liver stiffness from baseline assessed by Fibroscan®
timeFrame: 24 weeks
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Indianapolis
country: United States
facility: Indiana University- Adults
state: Indiana
city: St. Louis
country: United States
facility: St. Louis University
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Liver Institute Northwest
state: Washington
Study officials:
affiliation: Virginia Commonwealth University
name: Arun Sanyal, MD
role: PRINCIPAL_INVESTIGATOR
References: