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

Lifestyle Intervention and Antioxidants in Children With Nonalcoholic Fatty Liver Disease: A Randomized, Controlled Trial

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Rome, Italy, 00165
        • Dept. Of HepatoGastoEnterology and Nutrition, Liver Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 20 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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].
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 Names:
  • 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].
placebo and lifestyle intervention [hypocaloric Diet(25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity].

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
serum levels of aminotransferases
Time Frame: months 12 and 24
months 12 and 24

Secondary Outcome Measures

Outcome Measure
Time Frame
Liver histology (inflammation and fibrosis)
Time Frame: month 24
month 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Valerio Nobili, MD, Bambino Gesù Hospital and Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2003

Primary Completion (Actual)

October 1, 2006

Study Completion (Actual)

October 1, 2006

Study Registration Dates

First Submitted

April 3, 2008

First Submitted That Met QC Criteria

April 8, 2008

First Posted (Estimate)

April 9, 2008

Study Record Updates

Last Update Posted (Estimate)

April 9, 2008

Last Update Submitted That Met QC Criteria

April 8, 2008

Last Verified

March 1, 2008

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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