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Completed

NCT Number: NCT00063635

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.

Completed

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Key information

Conditions

Fatty Liver Digestive System Diseases Liver Diseases Non-alcoholic Fatty Liver Disease

Age range

8 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University of California, San Diego, San Diego, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

  • 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

Treatment and study plan

metformin

Drug

500 mg, twice daily

Vitamin E

Dietary Supplement

400 IU, twice daily

Other names: Nature Made

Matching Placebo

Drug

Twice daily

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

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

Nih

Registry information

Official study title

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

Acronym: TONIC

Important dates

Study start
2005
Primary completion
2009
Study completion
2010
First posted
Jul 3, 2003
Registry last updated
Sep 27, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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