Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC) (TONIC)

August 27, 2012 updated by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Clinical Research Network in Nonalcoholic Steatohepatitis: Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)

The purpose of this study is to determine if therapeutic modification of insulin resistance or oxidative stress leads to improvement in serum or histologic indicators of liver injury or quality of life.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

173

Phase

  • 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

  • United States
    • California
      • San Diego, California, United States, 92103
        • University of California, San Diego
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Johns Hopkins University
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • St. Louis University
    • Ohio
      • Cleveland, Ohio, United States, 44109
        • Case Western Reserve University
    • Texas
      • Houston, Texas, United States, 77030
        • Texas Children's Hospital
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington

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

8 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • Age 8-17 years at first screening visit
  • Histologic evidence of Nonalcoholic Fatty Liver Disease (NAFLD) - biopsy cannot be older than 6 months as of randomization
  • ALT level >60 U/L at time of screening and on one previous occasion determined at least one month but no greater than 6 months prior to screening ALT
  • Consent

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 3
Matching placebo
Drug: Matching placebo
Twice daily
Active Comparator: 1
Metformin, 500 mg, twice daily
Drug: Metformin
500 mg, twice daily
Active Comparator: 2
Vitamin E, 400 IU, twice daily
Dietary supplement: Vitamin E
400 IU, twice daily
Other Names:
  • Nature Made

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Sustained Reduction in Alanine Aminotransferase (ALT) to Either 50% of Baseline Value or < 40 IU/L
Time Frame: baseline and 96 weeks
The primary outcome was sustained reduction in ALT level, defined as 50% or less of the baseline level or 40 IU/L or less at each visit from 48 to 96 weeks of treatment.
baseline and 96 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Serum Aspartate Aminotransferase (AST)
Time Frame: baseline and 96 weeks
baseline and 96 weeks
Change in Nonalcoholic Fatty Liver Disease (NAFLD) Score (Histologic Feature Scores Determined by Standardized Scoring of Liver Biopsies) From Baseline at 96 Weeks of Treatment
Time Frame: baseline and 96 weeks
Histological activity was assessed using the NAFLD activity score on a scale of 0 to 8, with higher scores indicating more severe disease; the components of this measure include steatosis (0-3), lobular inflammation (0-3), and hepatocellular ballooning (0-2).
baseline and 96 weeks
Number of Participants With Improvement in Liver Fibrosis Score
Time Frame: baseline and 96 weeks
Fibrosis is assessed on a scale of 0 to 4 with higher scores indicating more severe fibrosis. This secondary outcome measure is the number of participants that experienced a decrease in fibrosis score at 96 weeks compared to baseline, which indicates improvement in fibrosis.
baseline and 96 weeks
Number of Participants With Improvement in Steatosis Score
Time Frame: baseline and 96 weeks
Steatosis is assessed on a scale of 0 to 3 with higher scores indicating more severe steatosis. This secondary outcome measure is the number of participants that experienced a decrease in steatosis score at 96 weeks compared to baseline, which indicates improvement in steatosis.
baseline and 96 weeks
Number of Participants With Improvement in Lobular Inflammation Score
Time Frame: baseline and 96 weeks
Lobular inflammation is assessed on a scale of 0 to 3 with higher scores indicating more severe lobular inflammation. This secondary outcome measure is the number of participants that experienced a decrease in lobular inflammation score at 96 weeks compared to baseline, which indicates improvement in lobular inflammation.
baseline and 96 weeks
Number of Participants With Improvement in Ballooning Degradation Score
Time Frame: baseline and 96 weeks
Ballooning is assessed on a scale of 0 to 2 with higher scores indicating more severe ballooning. This secondary outcome measure is the number of participants that experienced a decrease in ballooning score at 96 weeks compared to baseline, which indicates improvement in ballooning.
baseline and 96 weeks
Change in Body Mass Index
Time Frame: baseline and 96 weeks
baseline and 96 weeks
Change in Serum Vitamin E Levels
Time Frame: baseline and 96 weeks
Change in alpha-Tocopherol
baseline and 96 weeks
Change in Quality of Life (QOL) Scores- Physical Health
Time Frame: baseline and 96 weeks
Change in self-reported QOL physical health Pediatric Quality of Life Inventory (version 4.0) scores were recorded to range from 0 to 100 with increasing scores indicating better quality of life.
baseline and 96 weeks
Change in QOL- Psychosocial Health
Time Frame: baseline and 96 weeks
Change in self-reported QOL physical health Pediatric Quality of Life Inventory (version 4.0) scores were recorded to range from 0 to 100 with increasing scores indicating better quality of life.
baseline and 96 weeks

Collaborators and Investigators

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

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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.

General Publications

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

September 1, 2005

Primary Completion (Actual)

September 1, 2009

Study Completion (Actual)

February 1, 2010

Study Registration Dates

First Submitted

July 1, 2003

First Submitted That Met QC Criteria

July 2, 2003

First Posted (Estimate)

July 3, 2003

Study Record Updates

Last Update Posted (Estimate)

September 27, 2012

Last Update Submitted That Met QC Criteria

August 27, 2012

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NASH - PEDIATRICS (IND)

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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