Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC) - Full Text View

Sponsor:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:	NCT00063635

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	Intervention	Phase
Fatty Liver	Drug: Metformin Dietary Supplement: Vitamin E Drug: Matching placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	Clinical Research Network in Nonalcoholic Steatohepatitis: Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines Liver Diseases Vitamin E

Drug Information available for: alpha-Tocopherol DL-alpha-Tocopherol Metformin Metformin hydrochloride Vitamin E Tocopherols Tocotrienol

U.S. FDA Resources

Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:

Sustained reduction in ALT to either 50% of baseline value or < 40 U/L [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Sustained reduction in serum AST [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
Sustained reduction in serum GGT [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
Change in histologic feature scores determined by standardized scoring of liver biopsies at baseline and after 96 weeks of treatment [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
Change in liver fibrosis, inflammation, or steatosis [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
Change in body mass index [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
Change in insulin resistance indices [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
Change in serum vitamin E levels [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
Change in serum lipid profile [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
Change in QOL scores [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]

Enrollment:	173
Study Start Date:	August 2005
Study Completion Date:	February 2010
Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Metformin, 500 mg, twice daily	Drug: Metformin 500 mg, twice daily
Active Comparator: 2 Vitamin E, 400 IU, twice daily	Dietary Supplement: Vitamin E 400 IU, twice daily Other Name: Nature Made
Placebo Comparator: 3 Matching placebo	Drug: Matching placebo Twice daily

Eligibility

Ages Eligible for Study:	8 Years to 17 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00063635

Locations

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

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

More Information

Additional Information:

National Institute of Diabetes and Digestive and Kidney Diseases This link exits the ClinicalTrials.gov site

No publications provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, Abrams SH, Scheimann AO, Sanyal AJ, Chalasani N, Tonascia J, Ünalp 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.

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. Epub 2009 Sep 15.

Responsible Party:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:	NCT00063635 History of Changes
Other Study ID Numbers:	NASH - PEDIATRICS (IND)
Study First Received:	July 1, 2003
Last Updated:	December 21, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Non alcoholic fatty liver disease

Additional relevant MeSH terms:

Fatty Liver
Liver Diseases
Digestive System Diseases
Metformin
Vitamin E
Alpha-Tocopherol
Tocopherols
Tocotrienols
Vitamins

Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on February 12, 2012