Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC) (TONIC)
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ClinicalTrials.gov Identifier: NCT00063635 |
Recruitment Status :
Completed
First Posted : July 3, 2003
Results First Posted : September 27, 2012
Last Update Posted : September 27, 2012
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Fatty Liver | Drug: Metformin Dietary Supplement: Vitamin E Drug: Matching placebo | Phase 3 |
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 |

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 |
- 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.
- Change in Serum Aspartate Aminotransferase (AST) [ Time Frame: 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).
- 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.
- 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.
- 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.
- 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.
- Change in Body Mass Index [ Time Frame: baseline and 96 weeks ]
- Change in Serum Vitamin E Levels [ Time Frame: baseline and 96 weeks ]Change in alpha-Tocopherol
- 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.
- 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.

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Ages Eligible for Study: | 8 Years to 17 Years (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
- 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

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
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 |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 |
Non alcoholic fatty liver disease |
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 |