Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)
TONIC
Clinical Research Network in Nonalcoholic Steatohepatitis: Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)
1 other identifier
interventional
173
1 country
10
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Sep 2005
Typical duration for phase_3
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 1, 2003
CompletedFirst Posted
Study publicly available on registry
July 3, 2003
CompletedStudy Start
First participant enrolled
September 1, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2010
CompletedResults Posted
Study results publicly available
September 27, 2012
CompletedSeptember 27, 2012
August 1, 2012
4 years
July 1, 2003
June 26, 2012
August 27, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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
Secondary Outcomes (10)
Change in Serum Aspartate Aminotransferase (AST)
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
baseline and 96 weeks
Number of Participants With Improvement in Liver Fibrosis Score
baseline and 96 weeks
Number of Participants With Improvement in Steatosis Score
baseline and 96 weeks
Number of Participants With Improvement in Lobular Inflammation Score
baseline and 96 weeks
- +5 more secondary outcomes
Study Arms (3)
1
ACTIVE COMPARATORMetformin, 500 mg, twice daily
2
ACTIVE COMPARATORVitamin E, 400 IU, twice daily
3
PLACEBO COMPARATORMatching placebo
Interventions
Eligibility Criteria
Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.
Sponsors & Collaborators
Study Sites (10)
University of California, San Diego
San Diego, California, 92103, United States
University of California, San Francisco
San Francisco, California, 94143, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Indiana University
Indianapolis, Indiana, 46202, United States
Johns Hopkins University
Baltimore, Maryland, 21205, United States
St. Louis University
St Louis, Missouri, 63110, United States
Case Western Reserve University
Cleveland, Ohio, 44109, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
University of Washington
Seattle, Washington, 98195, United States
Related Publications (4)
Corey KE, Vuppalanchi R, Vos M, Kohli R, Molleston JP, Wilson L, Unalp-Arida A, Cummings OW, Lavine JE, Chalasani N; Nonalcoholic Steatohepatitis Clinical Research Network. Improvement in liver histology is associated with reduction in dyslipidemia in children with nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. 2015 Mar;60(3):360-7. doi: 10.1097/MPG.0000000000000584.
PMID: 25714579DERIVEDGuerrerio AL, Colvin RM, Schwartz AK, Molleston JP, Murray KF, Diehl A, Mohan P, Schwimmer JB, Lavine JE, Torbenson MS, Scheimann AO. Choline intake in a large cohort of patients with nonalcoholic fatty liver disease. Am J Clin Nutr. 2012 Apr;95(4):892-900. doi: 10.3945/ajcn.111.020156. Epub 2012 Feb 15.
PMID: 22338037DERIVEDLavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, Abrams SH, Scheimann AO, Sanyal AJ, Chalasani N, Tonascia J, Unalp A, Clark JM, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR; Nonalcoholic Steatohepatitis Clinical Research Network. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA. 2011 Apr 27;305(16):1659-68. doi: 10.1001/jama.2011.520.
PMID: 21521847DERIVEDLavine JE, Schwimmer JB, Molleston JP, Scheimann AO, Murray KF, Abrams SH, Rosenthal P, Sanyal AJ, Robuck PR, Brunt EM, Unalp A, Tonascia J; Nonalcoholic Steatohepatitis Clinical Research Network Research Group. Treatment of nonalcoholic fatty liver disease in children: TONIC trial design. Contemp Clin Trials. 2010 Jan;31(1):62-70. doi: 10.1016/j.cct.2009.09.001. Epub 2009 Sep 15.
PMID: 19761871DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Joel E. Lavine, MD, PhD
- Organization
- Columbia University Medical Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 1, 2003
First Posted
July 3, 2003
Study Start
September 1, 2005
Primary Completion
September 1, 2009
Study Completion
February 1, 2010
Last Updated
September 27, 2012
Results First Posted
September 27, 2012
Record last verified: 2012-08