Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)
This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00063635
First received: July 1, 2003
Last updated: August 27, 2012
Last verified: August 2012
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Fatty Liver |
Drug: Metformin Dietary Supplement: Vitamin E Drug: Matching placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | Clinical Research Network in Nonalcoholic Steatohepatitis: Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC) |
Resource links provided by NLM:
Drug Information available for:
alpha-Tocopherol
Metformin
Metformin hydrochloride
Tocopherol
Vitamin E succinate
Tocopherol acetate
dl-alpha-Tocopherol
U.S. FDA Resources
Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Primary Outcome Measures:
- 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 ] [ Designated as safety issue: No ]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:
- Change in Serum Aspartate Aminotransferase (AST) [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
- Change in Serum Vitamin E Levels [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]Change in alpha-Tocopherol
- Change in Quality of Life (QOL) Scores- Physical Health [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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.
| Enrollment: | 173 |
| Study Start Date: | September 2005 |
| Study Completion Date: | February 2010 |
| Primary Completion Date: | September 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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
|
Eligibility| Ages Eligible for Study: | 8 Years to 17 Years |
| Genders Eligible for Study: | Both |
| 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00063635
Locations
| 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
More Information
Additional Information:
No publications provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Additional 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 History of Changes |
| Other Study ID Numbers: | NASH - PEDIATRICS (IND) |
| Study First Received: | July 1, 2003 |
| Results First Received: | June 26, 2012 |
| Last Updated: | August 27, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
|
Non alcoholic fatty liver disease |
Additional relevant MeSH terms:
|
Fatty Liver Liver Diseases Digestive System Diseases Metformin Vitamin E Alpha-Tocopherol Tocopherols Tocotrienols Vitamins |
Hypoglycemic Agents Physiological Effects of Drugs Pharmacologic Actions Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Micronutrients Growth Substances |
ClinicalTrials.gov processed this record on May 16, 2013