Effect of Vitamin E on Pediatric Nonalcoholic Fatty Liver Disease (NAFLD)
Condition: Inflammation; Fibrosis; Insulin Resistance
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Insulin Resistance; Inflammation
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      No proven treatment exists for nonalcoholic fatty liver disease (NAFLD) in children and
      adolescents. We aim to determine the efficacy of lifestyle intervention with or without
      antioxidant therapy in pediatric NAFLD.
    

Detailed description: 
      InChildren or adolescents with well-characterized and liver biopsy confirmed NAFLD will be
      enrolled. They will be randomized to treatment with alpha tocopherol 600 IU/d plus ascorbic
      acid 500 mg/d (n=45) or an identical placebo (n=45) given orally. All patients will be
      included in a lifestyle intervention program consisting of a diet tailored on the individual
      requirements and physical exercise. The body mass index (BMI) and BMI Z-score will be
      calculated . Obesity was defined for a percentile of BMI ≥ 95th percentile for age and gender
      .

      Patients will undergo a medical evaluation every three months during the 24-month study
      period. Laboratory tests including liver enzymes and lipids will be repeated at 3-month
      intervals during the 24-month study duration. Ultrasonography of the liver will be repeated
      at the end of the study period.

      Evaluation of Glucose Metabolism and Insulin Sensitivity A 2-hour oral glucose tolerance test
      (OGTT) will be performed at baseline and repeated at 24 mo. of treatment with the standard
      1.75 g of glucose per kg, or maximum of 75 g. Glucose tolerance status will be determined
      according to the classification of the American Diabetes Association in which fasting plasma
      glucose (FPG) levels up to 99 mg/dl are considered normal; impaired fasting glucose (IFG) is
      defined by a FPG of 100-125 mg/dl; impaired glucose tolerance (IGT) is defined by a 2-hour
      plasma glucose of 140-199 mg/dl; diabetes mellitus is defined by a FPG ≥126 mg/dl, or a
      2-hour plasma glucose ≥200 mg/dl .

      The degrees of insulin resistance and sensitivity will be determined, respectively, by the
      homeostatic model assessment (HOMA-IR) using the formula: IR = (insulin*glucose)/22.5; and by
      the insulin sensitivity index (ISI) derived from OGTT using the formula: ISI = (10,000/square
      root of [fasting glucose x fasting insulin] x [mean glucose x mean insulin during OGTT]).

      Liver biopsy Liver biopsy will be performed at baseline and repeated at 24 mo. of treatment.
      Biopsies will be routinely processed and analyzed as described previously. Pre- and
      post-treatment liver biopsies will be reviewed and scored by a single pathologist who will be
      unaware of the assigned treatment, patients' clinical and laboratory data, and liver biopsy
      sequence. The main histological features of NAFLD including steatosis (macro and
      microvesicular), inflammation (portal and lobular), hepatocyte ballooning, and fibrosis will
      be scored using the scoring system for NAFLD recently proposed by the NIH-sponsored NASH
      Clinical Research Network.
    

Intervention name(s): Vitamin treatment (alpha tocopherol plus ascorbic acid); Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): alpha tocopherol 600 IU/d plus ascorbic acid 500 mg/d and lifestyle intervention [hypocaloric Diet(25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity].; placebo and lifestyle intervention [hypocaloric Diet(25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity].
Other intervention name(s): alpha-tocoferol
Intervention MeSH terms: Ascorbic Acid; Tocopherols; Vitamin E; alpha-Tocopherol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Non-Alcoholic Fatty Liver Disease (NAFLD); Non-Alcoholic Steatohepatitis (NASH); Liver histology; Insulin Resistance; Weight loss; Alpha-tocopherol; ascorbic acid