Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC) | RxWiki

Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)

Overview[ - collapse ][ - ]

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	Fatty Liver
Intervention	Drug: Metformin Dietary Supplement: Vitamin E Drug: Matching placebo
Phase	Phase 3
Sponsor	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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

Tracking Information[ + expand ][ + ]

First Received Date	July 1, 2003
Last Updated Date	August 27, 2012
Start Date	September 2005
Estimated Primary Completion Date	February 2010
Current 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.
Current 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.

Descriptive Information[ + expand ][ + ]

Brief Title	Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)
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 Description	Not Provided
Study Type	Interventional
Study Phase	Phase 3
Study Design	Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Condition	Fatty Liver
Intervention	Drug: Metformin 500 mg, twice daily Dietary Supplement: Vitamin E 400 IU, twice daily Other Names: Nature MadeDrug: Matching placebo Twice daily
Study Arm (s)	Active Comparator: 1 Metformin, 500 mg, twice daily Active Comparator: 2 Vitamin E, 400 IU, twice daily Placebo Comparator: 3 Matching placebo

Recruitment Information[ + expand ][ + ]

Recruitment Status	Completed
Estimated Enrollment	173
Estimated Completion Date	February 2010
Estimated Primary Completion Date	September 2009
Eligibility 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
Gender	Both
Ages	8 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT00063635
Other Study ID Numbers	NASH - PEDIATRICS (IND)
Has Data Monitoring Committee	Yes
Information Provided By	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study Sponsor	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators	Not Provided
Investigators	Not Provided
Verification Date	August 2012

Locations[ + expand ][ + ]

University of California, San Diego	San Diego, California, United States, 92103
University of California, San Francisco	San Francisco, California, United States, 94143
Children's National Medical Center	Washington, District of Columbia, United States, 20010
Indiana University	Indianapolis, Indiana, United States, 46202
Johns Hopkins University	Baltimore, Maryland, United States, 21205
St. Louis University	St. Louis, Missouri, United States, 63110
Case Western Reserve University	Cleveland, Ohio, United States, 44109
Texas Children's Hospital	Houston, Texas, United States, 77030
Virginia Commonwealth University	Richmond, Virginia, United States, 23298
University of Washington	Seattle, Washington, United States, 98195