Vitamin E Dosing Study

Nonalcoholic Steatohepatitis Clinical Trial

— VEDS  

Official title:

Vitamin E Dosing Study (VEDS): A Dose Finding Study of Vitamin E for the Treatment of Adult NAFLD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04801849
• Other study ID #: 10 VEDS
• Secondary ID: U24DK061730U01DK
• Status: Recruiting
• Phase: Phase 2
• Start date: August 5, 2022
• Est. completion date: August 30, 2025

Study information

• Verified date: November 2023
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: Emily Mitchell, MS, MBA
• Phone: 410-955-8183
• Email: esharke5[@]jhu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: August 30, 2025
• Est. primary completion date: February 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis

Intervention

Drug:
• 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
• Placebo
Participants will take a placebo vitamin E capsule daily for 24 weeks

Locations

Country	Name	City	State
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Indiana University- Adults	Indianapolis	Indiana
United States	University of California, San Diego	La Jolla	California
United States	University of Southern California	Los Angeles	California
United States	Virginia Commonwealth University	Richmond	Virginia
United States	St. Louis University	Saint Louis	Missouri
United States	University of California, San Francisco	San Francisco	California
United States	Liver Institute Northwest	Seattle	Washington

Sponsors (10)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Duke University, Indiana University, Liver Institute Northwest, St. Louis University, The Cleveland Clinic, University of California, San Diego, University of California, San Francisco, University of Southern California, Virginia Commonwealth University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative change in alanine aminotransferase (ALT) from baseline to 24 weeks	ALT value in units/liter (U/L)	24 weeks
Secondary	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.	24 weeks
Secondary	Mean change in serum alanine aminotransferase (ALT) from baseline	ALT value in U/L	24 weeks
Secondary	Mean change in serum aspartate aminotransferase (AST) from baseline	AST value in U/L	24 weeks
Secondary	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	24 weeks
Secondary	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).	24 weeks

External Links

•   Nonalcoholic Steatohepatitis Clinical Research Network Centers
•   The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)