Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)

Phase 3

Completed

• Conditions: Fatty Liver
• Interventions: Drug: Matching placebo; Dietary Supplement: Vitamin E; Drug: Metformin

• Registration Number: NCT00063635
• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2003-07-01
• Study First Submitted QC: 2003-07-02
• Study First Posted: 2003-07-03
• Study Start: 2005-09
• Primary Completion: 2009-09
• Study Completion: 2010-02
• Results First Submitted: 2012-06-26
• Status Verified: 2012-08
• Results First Submitted QC: 2012-08-27
• Last Update Submitted: 2012-08-27
• Results First Posted: 2012-09-27
• Last Update Posted: 2012-09-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 173

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
3	Matching placebo	Matching placebo
2	Vitamin E	Vitamin E, 400 IU, twice daily
1	Metformin	Metformin, 500 mg, twice daily

Primary Outcome Measures

Name	Time	Method
Number of Participants With Sustained Reduction in Alanine Aminotransferase (ALT) to Either 50% of Baseline Value or < 40 IU/L	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

Name	Time	Method
Change in Body Mass Index	baseline and 96 weeks
Change in Serum Aspartate Aminotransferase (AST)	baseline and 96 weeks
Number of Participants With Improvement in Liver Fibrosis Score	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.
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	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 Ballooning Degradation Score	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.
Number of Participants With Improvement in Steatosis Score	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	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.
Change in Serum Vitamin E Levels	baseline and 96 weeks	Change in alpha-Tocopherol
Change in Quality of Life (QOL) Scores- Physical Health	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	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.

Trial Locations

Locations (10)

University of California, San Diego; 🇺🇸 San Diego, California, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

St. Louis University; 🇺🇸 St. Louis, Missouri, United States

Case Western Reserve University; 🇺🇸 Cleveland, Ohio, United States

Texas Children's Hospital; 🇺🇸 Houston, Texas, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

University of Washington; 🇺🇸 Seattle, Washington, United States