Clinical trial NCT00063635: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fatty Liver
Keywords: Non alcoholic fatty liver disease
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
First posted: 2003-07-03
Enrollment: 173
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Sustained Reduction in Alanine Aminotransferase (ALT) to Either 50% of Baseline Value or < 40 IU/L
timeFrame: baseline and 96 weeks
Secondary outcomes:
measure: Change in Serum Aspartate Aminotransferase (AST)
timeFrame: baseline and 96 weeks
measure: 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
timeFrame: baseline and 96 weeks
measure: Number of Participants With Improvement in Liver Fibrosis Score
timeFrame: baseline and 96 weeks
measure: Number of Participants With Improvement in Steatosis Score
timeFrame: baseline and 96 weeks
measure: Number of Participants With Improvement in Lobular Inflammation Score
timeFrame: baseline and 96 weeks
measure: Number of Participants With Improvement in Ballooning Degradation Score
timeFrame: baseline and 96 weeks
measure: Change in Body Mass Index
timeFrame: baseline and 96 weeks
measure: Change in Serum Vitamin E Levels
timeFrame: baseline and 96 weeks
measure: Change in Quality of Life (QOL) Scores- Physical Health
timeFrame: baseline and 96 weeks
measure: Change in QOL- Psychosocial Health
timeFrame: baseline and 96 weeks
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: St. Louis
country: United States
facility: St. Louis University
state: Missouri
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
References:
citation: 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.
citation: Guerrerio 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.
citation: Lavine 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.
citation: Lavine 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.