Effect of Vitamin E on Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) (VITENAFLD)

This study has been completed.
Sponsor:
Information provided by:
Bambino Gesù Hospital and Research Institute
ClinicalTrials.gov Identifier:
NCT00655018
First received: April 3, 2008
Last updated: April 8, 2008
Last verified: March 2008
  Purpose

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.


Condition Intervention Phase
Inflammation
Fibrosis
Insulin Resistance
Dietary Supplement: Vitamin treatment (alpha tocopherol plus ascorbic acid)
Dietary Supplement: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Lifestyle Intervention and Antioxidants in Children With Nonalcoholic Fatty Liver Disease: A Randomized, Controlled Trial

Resource links provided by NLM:


Further study details as provided by Bambino Gesù Hospital and Research Institute:

Primary Outcome Measures:
  • serum levels of aminotransferases [ Time Frame: months 12 and 24 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Liver histology (inflammation and fibrosis) [ Time Frame: month 24 ] [ Designated as safety issue: No ]

Enrollment: 90
Study Start Date: January 2003
Study Completion Date: October 2006
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vitamin group
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].
Dietary Supplement: Vitamin treatment (alpha tocopherol plus ascorbic acid)
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].
Other Name: alpha-tocoferol
Placebo Comparator: 2
placebo and lifestyle intervention [hypocaloric Diet(25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity].
Dietary Supplement: Placebo
placebo and lifestyle intervention [hypocaloric Diet(25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity].

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.

  Eligibility

Ages Eligible for Study:   3 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • persistently elevated serum aminotransferase levels,
  • diffusely echogenic liver on imaging studies suggestive of fatty liver, and
  • biopsy consistent with the diagnosis of NAFLD.

Exclusion Criteria:

  • hepatic virus infections (HCV RNA-PCR negative),
  • Hepatitis A, B, C, D, E and G,
  • cytomegalovirus and Epstein-Barr virus,
  • alcohol consumption,
  • history of parenteral nutrition,
  • and use of drugs known to induce steatosis (e.g. valproate, amiodarone or prednisone) or to affect body weight and carbohydrate metabolism.
  • Autoimmune liver disease, metabolic liver disease, Wilson's disease, and a-1-antitrypsin-associated liver disease were ruled out using standard clinical, laboratory and histological criteria.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00655018

Locations
Italy
Dept. Of HepatoGastoEnterology and Nutrition, Liver Unit
Rome, Italy, 00165
Sponsors and Collaborators
Bambino Gesù Hospital and Research Institute
Investigators
Principal Investigator: Valerio Nobili, MD Bambino Gesù Hospital and Research Institute
  More Information

Additional Information:
Publications:
Responsible Party: Valerio Nobili, MD, Bambino Gesù Hospital and Research Institute
ClinicalTrials.gov Identifier: NCT00655018     History of Changes
Other Study ID Numbers: VITENAFLD
Study First Received: April 3, 2008
Last Updated: April 8, 2008
Health Authority: Italy: Ethics Committee

Keywords provided by Bambino Gesù Hospital and Research Institute:
Non-Alcoholic Fatty Liver Disease (NAFLD)
Non-Alcoholic Steatohepatitis (NASH)
Liver histology
Insulin Resistance
Weight loss
Alpha-tocopherol
ascorbic acid

Additional relevant MeSH terms:
Fatty Liver
Fibrosis
Inflammation
Insulin Resistance
Liver Diseases
Digestive System Diseases
Pathologic Processes
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Ascorbic Acid
Tocopherols
Vitamin E
Alpha-Tocopherol
Tocotrienols
Vitamins
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on April 16, 2014