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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00063635
Recruitment Status : Completed
First Posted : July 3, 2003
Results First Posted : September 27, 2012
Last Update Posted : September 27, 2012
Sponsor:
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Fatty Liver Drug: Metformin Dietary Supplement: Vitamin E Drug: Matching placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 173 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Clinical Research Network in Nonalcoholic Steatohepatitis: Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)
Study Start Date : September 2005
Actual Primary Completion Date : September 2009
Actual Study Completion Date : February 2010

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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 Name: Nature Made
Placebo Comparator: 3
Matching placebo
 Drug: Matching placebo
Twice daily


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Change in Serum Aspartate Aminotransferase (AST) [ Time Frame: baseline and 96 weeks ]
  2. 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).

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Change in Body Mass Index [ Time Frame: baseline and 96 weeks ]
  8. Change in Serum Vitamin E Levels [ Time Frame: baseline and 96 weeks ]
    Change in alpha-Tocopherol

  9. 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.

  10. 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.


Eligibility Criteria
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Ages Eligible for Study:   8 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00063635


Locations
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United States, California
University of California, San Diego
San Diego, California, United States, 92103
University of California, San Francisco
San Francisco, California, United States, 94143
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21205
United States, Missouri
St. Louis University
St. Louis, Missouri, United States, 63110
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44109
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00063635    
Other Study ID Numbers: NASH - PEDIATRICS (IND)
First Posted: July 3, 2003    Key Record Dates
Results First Posted: September 27, 2012
Last Update Posted: September 27, 2012
Last Verified: August 2012
Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Non alcoholic fatty liver disease
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Vitamin E
Metformin
Vitamins
 Micronutrients
Physiological Effects of Drugs
Hypoglycemic Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents