Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)

Fatty Liver Clinical Trial

— TONIC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00063635
• Other study ID #: NASH - PEDIATRICS (IND)
• Status: Completed
• Phase: Phase 3
• First received: July 1, 2003
• Last updated: August 27, 2012
• Start date: September 2005
• Est. completion date: February 2010

Study information

• Verified date: August 2012
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 173
• Est. completion date: February 2010
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 8 Years to 17 Years

Eligibility

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases

Intervention

Drug:
• Metformin
500 mg, twice daily

Dietary Supplement:
• Vitamin E
400 IU, twice daily

Drug:
• Matching placebo
Twice daily

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	Case Western Reserve University	Cleveland	Ohio
United States	Texas Children's Hospital	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of California, San Diego	San Diego	California
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington	Seattle	Washington
United States	St. Louis University	St. Louis	Missouri
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Sustained Reduction in Alanine Aminotransferase (ALT) to Either 50% of Baseline Value or < 40 IU/L	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.	baseline and 96 weeks	No
Secondary	Change in Serum Aspartate Aminotransferase (AST)		baseline and 96 weeks	No
Secondary	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	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).	baseline and 96 weeks	No
Secondary	Number of Participants With Improvement in Liver Fibrosis Score	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.	baseline and 96 weeks	No
Secondary	Number of Participants With Improvement in Steatosis Score	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.	baseline and 96 weeks	No
Secondary	Number of Participants With Improvement in Lobular Inflammation Score	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.	baseline and 96 weeks	No
Secondary	Number of Participants With Improvement in Ballooning Degradation Score	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.	baseline and 96 weeks	No
Secondary	Change in Body Mass Index		baseline and 96 weeks	No
Secondary	Change in Serum Vitamin E Levels	Change in alpha-Tocopherol	baseline and 96 weeks	No
Secondary	Change in Quality of Life (QOL) Scores- Physical Health	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.	baseline and 96 weeks	No
Secondary	Change in QOL- Psychosocial Health	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.	baseline and 96 weeks	No

External Links

•   National Institute of Diabetes and Digestive and Kidney Diseases