Clinical Trial: Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Current Primary Outcome: 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.


Original Primary Outcome:

Current Secondary Outcome:

  • 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.


Original Secondary Outcome:

Information By: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Dates:
Date Received: July 1, 2003
Date Started: September 2005
Date Completion:
Last Updated: August 27, 2012
Last Verified: August 2012