Vitamin E Dosing Study (VEDS)

N
Naga Chalasani, MD

Primary Investigator

Administratively Closed
18 years or above
All
Phase 2
200 participants needed
2 Locations

Brief description of study

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 of study

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 primarybjective 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 of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis
  • Age: 18 years or above
  • Gender: All

Inclusion Criteria:

  • 18 years of age or older as of the initial screening interview and provision of
  • 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/day
  • Current or history of significant alcohol consumption for a period of more than 3utive months within 1 year prior to screening (significant alcohol consumptiondefined as more than 20 g/day (~1.5 drinks/day) (> 10.5 drinks per week) in femalesd more than 30 g/day (~2 drinks/day) (>14 drinks per week) in males, respectively."standard" drink (or one alcoholic drink equivalent) contains roughly 14 grams ofure alcohol, which is found in: 12 ounces of regular beer, 5 ounces of wine, or 1.5unces of distilled spirits).
  • Inability to reliably quantify alcohol consumption based upon local study physicianjudgment
  • Continued use of drugs historically associated with NAFLD (amiodarone, methotrexate,ystemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater thanhose used for hormone replacement, anabolic steroids, valproic acid, and other knownhepatotoxins) for more than 2 weeks in the 6 months prior to randomization
  • Current use of anticoagulation therapy (not including antiplatelet agents such asdogrel)
  • 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,ux-en-Y gastric bypass)
  • Uncontrolled diabetes defined as HbA1c 9.5% or higher within 60 days prior todomization
  • Clinical evidence of hepatic decompensation as defined by the presence of any of thewing 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 liverhistology
    • Primary biliary cirrhosis as defined by the presence of at least 2 of these(i) Biochemical evidence of cholestasis based mainly on alkalinehosphatase elevation (ii) Presence of anti-mitochondrial antibody (AMA) (iii)Histologic evidence of nonsuppurative destructive cholangitis and destruction ofbular bile ducts[1]
    • Primary sclerosing cholangitis
    • Known history of Wilson disease, alpha-1-antitrypsin liver disease, orhemochromatosis. Any other type of liver disease that is currently active otherhan NASH such as drug-induced liver disease, liver cancer, or bile ductbstruction.
  • 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 < 60g/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 tog
  • Pregnancy, planned pregnancy, potential for pregnancy and unwillingness to use ≥ 1ve 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 withy age (younger than age 65).
    • Age 40 or older with more than one first-degree relative who had prostate cancery 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 compliancehinder completion of the study, including inability to swallow treatment capsules
  • Failure or inability to give informed consent

Updated on 13 Dec 2024. Study ID: 10 VEDS, GI-NIDDK-VEDS, 13746

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