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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
Sponsor:
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Tracking Information
First Submitted Date  ICMJE July 1, 2003
First Posted Date  ICMJE July 3, 2003
Results First Submitted Date  ICMJE June 26, 2012
Results First Posted Date  ICMJE September 27, 2012
Last Update Posted Date September 27, 2012
Study Start Date  ICMJE September 2005
Actual Primary Completion Date September 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 27, 2012)
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 Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2012)
  • 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 Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)
Official Title  ICMJE 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 Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Fatty Liver
Intervention  ICMJE
  • Drug: Metformin
    500 mg, twice daily
  • Dietary Supplement: Vitamin E
    400 IU, twice daily
    Other Name: Nature Made
  • Drug: Matching placebo
    Twice daily
Study Arms  ICMJE
  • Active Comparator: 1
    Metformin, 500 mg, twice daily
    Intervention: Drug: Metformin
  • Active Comparator: 2
    Vitamin E, 400 IU, twice daily
    Intervention: Dietary Supplement: Vitamin E
  • Placebo Comparator: 3
    Matching placebo
    Intervention: Drug: Matching placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 21, 2011)
173
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
150
Actual Study Completion Date  ICMJE February 2010
Actual Primary Completion Date September 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 8 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00063635
Other Study ID Numbers  ICMJE NASH - PEDIATRICS (IND)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study Sponsor  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Verification Date August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP