Trial · NCT00063635

Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)

NCT00063635, Phase 3, Completed, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); results first posted 2012-09-27

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ConductScience Library. Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC). Trials, record NCT00063635. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT00063635

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)
NCT number: NCT00063635
Status: Completed
Phases: Phase 3
Enrollment: 173 participants, actual
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Conditions: Fatty Liver
Interventions: Metformin, Vitamin E, Matching placebo
First posted: 2003-07-03
Last updated: 2012-09-27
Results first posted: 2012-09-27

Source ClinicalTrials.gov

Registered outcomes11

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Number of Participants With Sustained Reduction in Alanine Aminotransferase (ALT) to Either 50% of Baseline Value or < 40 IU/L	baseline and 96 weeks	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.
Secondary	Change in Serum Aspartate Aminotransferase (AST)	baseline and 96 weeks
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	baseline and 96 weeks	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).
Secondary	Number of Participants With Improvement in Liver Fibrosis Score	baseline and 96 weeks	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.
Secondary	Number of Participants With Improvement in Steatosis Score	baseline and 96 weeks	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.
Secondary	Number of Participants With Improvement in Lobular Inflammation Score	baseline and 96 weeks	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.
Secondary	Number of Participants With Improvement in Ballooning Degradation Score	baseline and 96 weeks	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.
Secondary	Change in Body Mass Index	baseline and 96 weeks
Secondary	Change in Serum Vitamin E Levels	baseline and 96 weeks	Change in alpha-Tocopherol
Secondary	Change in Quality of Life (QOL) Scores- Physical Health	baseline and 96 weeks	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.

1 to 10 of 11Source ClinicalTrials.gov

See all 11 registered outcomes

Outcomes11

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Number of Participants With Sustained Reduction in Alanine Aminotransferase (ALT) to Either 50% of Baseline Value or < 40 IU/L	baseline and 96 weeks	All enrolled patients were included in analysis of the primary outcome, sustained reduction in ALT level. Patients missing a 96-week ALT measurement were imputed as not achieving a sustained reduction.	participants	NUMBER
SECONDARY	Change in Serum Aspartate Aminotransferase (AST)	baseline and 96 weeks		IU/L	MEAN
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	baseline and 96 weeks	Number of participants analyzed reflects the number of participants with baseline and 96 week liver biopsies.	units on a scale	MEAN
SECONDARY	Number of Participants With Improvement in Liver Fibrosis Score	baseline and 96 weeks	Number of participants analyzed reflects the number of participants with baseline and 96 week liver biopsies.	participants	NUMBER
SECONDARY	Number of Participants With Improvement in Steatosis Score	baseline and 96 weeks	Number of participants analyzed reflects the number of participants with baseline and 96 week liver biopsies.	participants	NUMBER
SECONDARY	Number of Participants With Improvement in Lobular Inflammation Score	baseline and 96 weeks	Number of participants analyzed reflects the number of participants with baseline and 96 week liver biopsies.	participants	NUMBER
SECONDARY	Number of Participants With Improvement in Ballooning Degradation Score	baseline and 96 weeks	Number of participants analyzed reflects the number of participants with baseline and 96 week liver biopsies.	participants	NUMBER
SECONDARY	Change in Body Mass Index	baseline and 96 weeks		kg/m-squared	MEAN
SECONDARY	Change in Serum Vitamin E Levels	baseline and 96 weeks		mg/L	MEAN
SECONDARY	Change in Quality of Life (QOL) Scores- Physical Health	baseline and 96 weeks		units on a scale	MEAN

1 to 10 of 11Source ClinicalTrials.gov

See all 11 outcomes

Results by group33

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Value	Spread	Units
Number of Participants With Sustained Reduction in Alanine Aminotransferase (ALT) to Either 50% of Baseline Value or < 40 IU/L	Metformin	9	7 to 28	participants
Number of Participants With Sustained Reduction in Alanine Aminotransferase (ALT) to Either 50% of Baseline Value or < 40 IU/L	Vitamin E	15	15 to 39	participants
Number of Participants With Sustained Reduction in Alanine Aminotransferase (ALT) to Either 50% of Baseline Value or < 40 IU/L	Placebo	10	9 to 29	participants
Change in Serum Aspartate Aminotransferase (AST)	Metformin	-21.5	95% Confidence Interval -34.6 to -8.4	IU/L
Change in Serum Aspartate Aminotransferase (AST)	Vitamin E	-22.8	95% Confidence Interval -33.3 to -12.3	IU/L
Change in Serum Aspartate Aminotransferase (AST)	Placebo	-20.4	95% Confidence Interval -32.7 to -8.0	IU/L
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	Metformin	-1.1	95% Confidence Interval -1.7 to -0.5	units on a scale
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	Vitamin E	-1.8	95% Confidence Interval -2.4 to -1.2	units on a scale
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	Placebo	-0.7	95% Confidence Interval -1.3 to -0.2	units on a scale
Number of Participants With Improvement in Liver Fibrosis Score	Metformin	22		participants

1 to 10 of 33Source ClinicalTrials.gov

See all 33 results by group

Participant flow9

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Metformin	57
Overall Study	STARTED	Vitamin E	58
Overall Study	STARTED	Placebo	58
Overall Study	COMPLETED	Metformin	51
Overall Study	COMPLETED	Vitamin E	50
Overall Study	COMPLETED	Placebo	49
Overall Study	NOT COMPLETED	Metformin	6
Overall Study	NOT COMPLETED	Vitamin E	8
Overall Study	NOT COMPLETED	Placebo	9

Source ClinicalTrials.gov

Adverse events45

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk
other	Unspecified- Mild	General disorders	Metformin	10	57
other	Unspecified- Mild	General disorders	Vitamin E	10	58
other	Unspecified- Mild	General disorders	Placebo	6	58
other	Unspecified- Moderate	General disorders	Metformin	7	57
other	Unspecified- Moderate	General disorders	Vitamin E	7	58
other	Unspecified- Moderate	General disorders	Placebo	12	58
serious	Airway constriction/bronchospasm	Respiratory, thoracic and mediastinal disorders	Metformin	0	57
serious	Airway constriction/bronchospasm	Respiratory, thoracic and mediastinal disorders	Vitamin E	1	58
serious	Airway constriction/bronchospasm	Respiratory, thoracic and mediastinal disorders	Placebo	1	58
serious	Appendicitis	Gastrointestinal disorders	Metformin	1	57

1 to 10 of 45Source ClinicalTrials.gov

See all 45 adverse events

Adverse event totals9

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Metformin
Total, all-cause mortality	Vitamin E
Total, all-cause mortality	Placebo
Total, other adverse events	Metformin	17	57
Total, other adverse events	Vitamin E	17	58
Total, other adverse events	Placebo	18	58
Total, serious adverse events	Metformin	7	57
Total, serious adverse events	Vitamin E	6	58
Total, serious adverse events	Placebo	14	58

Source ClinicalTrials.gov

Papers5

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
19761871	DERIVED	PubMed
21521847	DERIVED	PubMed
22338037	DERIVED	PubMed
25714579	DERIVED	PubMed
40434633	DERIVED	PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons0

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

None in this release.

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

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