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

NCT ID: NCT00655018

Last Updated: 2008-04-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-01-31

Study Completion Date

2006-10-31

Brief Summary

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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

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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.

Conditions

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Inflammation Fibrosis Insulin Resistance

Keywords

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Non-Alcoholic Fatty Liver Disease (NAFLD) Non-Alcoholic Steatohepatitis (NASH) Liver histology Insulin Resistance Weight loss Alpha-tocopherol ascorbic acid

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Vitamin group

alpha tocopherol 600 IU/d plus ascorbic acid 500 mg/d and lifestyle intervention \[hypocaloric Diet(25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity\].

Group Type EXPERIMENTAL

Vitamin treatment (alpha tocopherol plus ascorbic acid)

Intervention Type DIETARY_SUPPLEMENT

alpha tocopherol 600 IU/d plus ascorbic acid 500 mg/d and lifestyle intervention \[hypocaloric Diet(25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity\].

2

placebo and lifestyle intervention \[hypocaloric Diet(25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity\].

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DIETARY_SUPPLEMENT

placebo and lifestyle intervention \[hypocaloric Diet(25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity\].

Interventions

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Vitamin treatment (alpha tocopherol plus ascorbic acid)

alpha tocopherol 600 IU/d plus ascorbic acid 500 mg/d and lifestyle intervention \[hypocaloric Diet(25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity\].

Intervention Type DIETARY_SUPPLEMENT

Placebo

placebo and lifestyle intervention \[hypocaloric Diet(25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity\].

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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alpha-tocoferol

Eligibility Criteria

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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.
Minimum Eligible Age

3 Years

Maximum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bambino Gesù Hospital and Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Bambino Gesù Hospital and Research Institute

Principal Investigators

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Valerio Nobili, MD

Role: PRINCIPAL_INVESTIGATOR

Bambino Gesù Hospital and Research Institute

Locations

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Dept. Of HepatoGastoEnterology and Nutrition, Liver Unit

Rome, , Italy

Site Status

Countries

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Italy

References

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Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N, David E, Rizzetto M, Marchesini G. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol. 2005 May;100(5):1082-90. doi: 10.1111/j.1572-0241.2005.41583.x.

Reference Type BACKGROUND
PMID: 15842582 (View on PubMed)

Vajro P, Mandato C, Franzese A, Ciccimarra E, Lucariello S, Savoia M, Capuano G, Migliaro F. Vitamin E treatment in pediatric obesity-related liver disease: a randomized study. J Pediatr Gastroenterol Nutr. 2004 Jan;38(1):48-55. doi: 10.1097/00005176-200401000-00012.

Reference Type BACKGROUND
PMID: 14676594 (View on PubMed)

Lavine JE. Vitamin E treatment of nonalcoholic steatohepatitis in children: a pilot study. J Pediatr. 2000 Jun;136(6):734-8.

Reference Type BACKGROUND
PMID: 10839868 (View on PubMed)

Nobili V, Manco M, Devito R, Ciampalini P, Piemonte F, Marcellini M. Effect of vitamin E on aminotransferase levels and insulin resistance in children with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2006 Dec;24(11-12):1553-61. doi: 10.1111/j.1365-2036.2006.03161.x.

Reference Type RESULT
PMID: 17206944 (View on PubMed)

Related Links

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Other Identifiers

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VITENAFLD

Identifier Type: -

Identifier Source: org_study_id