Treatment of nonalcoholic fatty liver disease in children

TONIC trial design

Joel E. Lavine, Jeffrey B. Schwimmer, Jean Molleston, Ann O. Scheimann, Karen F. Murray, Stephanie H. Abrams, Philip Rosenthal, Arun J. Sanyal, Patricia R. Robuck, Elizabeth M. Brunt, Aynur Ünalp, Girish Subbarao

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) in children can lead to steatohepatitis, cirrhosis, and end-stage liver disease. The cause of NAFLD is unknown, but it is commonly associated with obesity, insulin resistance, and dyslipidemia. Objectives: TONIC is conducted to test whether treatment with metformin, an insulin sensitizer, or vitamin E, a naturally available antioxidant, will lead to improvements in biochemical and histological features of nondiabetic children with biopsy-proven NAFLD. Design: TONIC is a randomized, multicenter, double-masked, placebo-controlled trial of 96 weeks of treatment with metformin or vitamin E. The primary outcome measure chosen for the trial is improvement in serum alanine aminotransferase (ALT) levels with treatment as compared to placebo. An improvement in ALT is defined as reduction in serum ALT levels to below 50% of the baseline values or into the normal range (40 U/L or less) during the last 48 weeks of treatment. Histological improvement is defined by changes in liver histology between a baseline and end-of-treatment liver biopsy in regards to (1) steatohepatitis, (2) NAFLD Activity Score, consisting of scores for steatosis, lobular inflammation, and hepatocellular injury (ballooning), and (3) fibrosis score. Methods: Between September 2005 and September 2007, 173 children were enrolled into TONIC at 10 clinical centers in the United States. Participants were randomized to receive either metformin (500 mg b.i.d.), vitamin E (400 IU b.i.d.), or placebo for 96 weeks. This protocol was approved by all participating center Institutional Review Boards (IRBs) and an independent Data and Safety Monitoring Board (DSMB). (ClinicalTrials.gov number, NCT00063635.).

Original languageEnglish
Pages (from-to)62-70
Number of pages9
JournalContemporary Clinical Trials
Volume31
Issue number1
DOIs
StatePublished - Jan 2010

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Metformin
Alanine Transaminase
Vitamin E
Placebos
Fatty Liver
Fibrosis
Clinical Trials Data Monitoring Committees
Biopsy
Therapeutics
End Stage Liver Disease
Research Ethics Committees
Liver
Dyslipidemias
Serum
Insulin Resistance
Histology
Reference Values
Obesity
Antioxidants
Outcome Assessment (Health Care)

Keywords

  • Children
  • Metformin
  • Nonalcoholic fatty liver
  • Nonalcoholic steatohepatitis
  • Randomized controlled trial
  • RRR-α-tocopherol
  • Vitamin E

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Medicine(all)

Cite this

Treatment of nonalcoholic fatty liver disease in children : TONIC trial design. / Lavine, Joel E.; Schwimmer, Jeffrey B.; Molleston, Jean; Scheimann, Ann O.; Murray, Karen F.; Abrams, Stephanie H.; Rosenthal, Philip; Sanyal, Arun J.; Robuck, Patricia R.; Brunt, Elizabeth M.; Ünalp, Aynur; Subbarao, Girish.

In: Contemporary Clinical Trials, Vol. 31, No. 1, 01.2010, p. 62-70.

Research output: Contribution to journalArticle

Lavine, JE, Schwimmer, JB, Molleston, J, Scheimann, AO, Murray, KF, Abrams, SH, Rosenthal, P, Sanyal, AJ, Robuck, PR, Brunt, EM, Ünalp, A & Subbarao, G 2010, 'Treatment of nonalcoholic fatty liver disease in children: TONIC trial design', Contemporary Clinical Trials, vol. 31, no. 1, pp. 62-70. https://doi.org/10.1016/j.cct.2009.09.001
Lavine, Joel E. ; Schwimmer, Jeffrey B. ; Molleston, Jean ; Scheimann, Ann O. ; Murray, Karen F. ; Abrams, Stephanie H. ; Rosenthal, Philip ; Sanyal, Arun J. ; Robuck, Patricia R. ; Brunt, Elizabeth M. ; Ünalp, Aynur ; Subbarao, Girish. / Treatment of nonalcoholic fatty liver disease in children : TONIC trial design. In: Contemporary Clinical Trials. 2010 ; Vol. 31, No. 1. pp. 62-70.
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