Ignite Creation Date:
2025-12-24 @ 10:35 PM
Ignite Modification Date:
2025-12-25 @ 8:07 PM
Study NCT ID:
NCT00063635
Status:
COMPLETED
Last Update Posted:
2012-09-27
First Post:
2003-07-01
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D005234', 'term': 'Fatty Liver'}, {'id': 'D065626', 'term': 'Non-alcoholic Fatty Liver Disease'}], 'ancestors': [{'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008687', 'term': 'Metformin'}, {'id': 'D014810', 'term': 'Vitamin E'}], 'ancestors': [{'id': 'D001645', 'term': 'Biguanides'}, {'id': 'D006146', 'term': 'Guanidines'}, {'id': 'D000578', 'term': 'Amidines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D001578', 'term': 'Benzopyrans'}, {'id': 'D011714', 'term': 'Pyrans'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'jl3553@columbia.edu', 'title': 'Joel E. Lavine, MD, PhD', 'organization': 'Columbia University Medical Center'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Metformin', 'description': 'Metformin, 500 mg, twice daily', 'otherNumAtRisk': 57, 'otherNumAffected': 17, 'seriousNumAtRisk': 57, 'seriousNumAffected': 7}, {'id': 'EG001', 'title': 'Vitamin E', 'description': 'Vitamin E, 400 IU, twice daily', 'otherNumAtRisk': 58, 'otherNumAffected': 17, 'seriousNumAtRisk': 58, 'seriousNumAffected': 6}, {'id': 'EG002', 'title': 'Placebo', 'description': 'Matching placebo', 'otherNumAtRisk': 58, 'otherNumAffected': 18, 'seriousNumAtRisk': 58, 'seriousNumAffected': 14}], 'otherEvents': [{'term': 'Unspecified- Mild', 'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numAffected': 10}, {'groupId': 'EG001', 'numAtRisk': 58, 'numAffected': 10}, {'groupId': 'EG002', 'numAtRisk': 58, 'numAffected': 6}], 'organSystem': 'General disorders'}, {'term': 'Unspecified- Moderate', 'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numAffected': 7}, {'groupId': 'EG001', 'numAtRisk': 58, 'numAffected': 7}, {'groupId': 'EG002', 'numAtRisk': 58, 'numAffected': 12}], 'organSystem': 'General disorders'}], 'seriousEvents': [{'term': 'Airway constriction/bronchospasm', 'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 58, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 58, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders'}, {'term': 'Appendicitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 58, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 58, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders'}, {'term': 'Cholecystitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 58, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 58, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders'}, {'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 58, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 58, 'numAffected': 0}], 'organSystem': 'General disorders'}, {'term': 'Diabetes', 'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 58, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 58, 'numAffected': 1}], 'organSystem': 'Endocrine disorders'}, {'term': 'Elevated serum glucose', 'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 58, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 58, 'numAffected': 0}], 'organSystem': 'Endocrine disorders'}, {'term': 'Hepatobiliary/pancreas', 'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 58, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 58, 'numAffected': 5}], 'organSystem': 'Hepatobiliary disorders'}, {'term': 'Hepatotoxicity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 58, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 58, 'numAffected': 0}], 'organSystem': 'Hepatobiliary disorders'}, {'term': 'Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 58, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 58, 'numAffected': 1}], 'organSystem': 'General disorders'}, {'term': 'Syncope', 'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 58, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 58, 'numAffected': 1}], 'organSystem': 'Cardiac disorders'}, {'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 58, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 58, 'numAffected': 1}], 'organSystem': 'General disorders'}, {'term': 'Depression', 'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 58, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 58, 'numAffected': 2}], 'organSystem': 'General disorders'}, {'term': 'Suicide', 'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 58, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 58, 'numAffected': 0}], 'organSystem': 'General disorders'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Participants With Sustained Reduction in Alanine Aminotransferase (ALT) to Either 50% of Baseline Value or < 40 IU/L', 'denoms': [{'units': 'Participants', 'counts': [{'value': '57', 'groupId': 'OG000'}, {'value': '58', 'groupId': 'OG001'}, {'value': '58', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Metformin, 500 mg, twice daily'}, {'id': 'OG001', 'title': 'Vitamin E', 'description': 'Vitamin E, 400 IU, twice daily'}, {'id': 'OG002', 'title': 'Placebo', 'description': 'Matching placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '9', 'groupId': 'OG000', 'lowerLimit': '7', 'upperLimit': '28'}, {'value': '15', 'groupId': 'OG001', 'lowerLimit': '15', 'upperLimit': '39'}, {'value': '10', 'groupId': 'OG002', 'lowerLimit': '9', 'upperLimit': '29'}]}]}], 'analyses': [{'pValue': '0.26', 'groupIds': ['OG001', 'OG002'], 'ciPctValue': '95', 'pValueComment': 'Since two primary comparisons are planned, a P-value of 0.025 will be considered significant, applying a Bonferroni correction for multiple comparisons.', 'statisticalMethod': 'Mantel Haenszel', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.83', 'groupIds': ['OG000', 'OG002'], 'ciPctValue': '95', 'pValueComment': 'Since two primary comparisons are planned, a P-value of 0.025 will be considered significant, applying a Bonferroni correction for multiple comparisons.', 'statisticalMethod': 'Mantel Haenszel', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'NUMBER', 'timeFrame': 'baseline and 96 weeks', 'description': '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.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': '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.'}, {'type': 'SECONDARY', 'title': 'Change in Serum Aspartate Aminotransferase (AST)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '51', 'groupId': 'OG000'}, {'value': '50', 'groupId': 'OG001'}, {'value': '49', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Metformin, 500 mg, twice daily'}, {'id': 'OG001', 'title': 'Vitamin E', 'description': 'Vitamin E, 400 IU, twice daily'}, {'id': 'OG002', 'title': 'Placebo', 'description': 'Matching placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '-21.5', 'groupId': 'OG000', 'lowerLimit': '-34.6', 'upperLimit': '-8.4'}, {'value': '-22.8', 'groupId': 'OG001', 'lowerLimit': '-33.3', 'upperLimit': '-12.3'}, {'value': '-20.4', 'groupId': 'OG002', 'lowerLimit': '-32.7', 'upperLimit': '-8.0'}]}]}], 'analyses': [{'pValue': '0.32', 'groupIds': ['OG001', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.29', 'groupIds': ['OG000', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'baseline and 96 weeks', 'unitOfMeasure': 'IU/L', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': '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', 'denoms': [{'units': 'Participants', 'counts': [{'value': '50', 'groupId': 'OG000'}, {'value': '50', 'groupId': 'OG001'}, {'value': '47', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Metformin, 500 mg, twice daily'}, {'id': 'OG001', 'title': 'Vitamin E', 'description': 'Vitamin E, 400 IU, twice daily'}, {'id': 'OG002', 'title': 'Placebo', 'description': 'Matching placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.1', 'groupId': 'OG000', 'lowerLimit': '-1.7', 'upperLimit': '-0.5'}, {'value': '-1.8', 'groupId': 'OG001', 'lowerLimit': '-2.4', 'upperLimit': '-1.2'}, {'value': '-0.7', 'groupId': 'OG002', 'lowerLimit': '-1.3', 'upperLimit': '-0.2'}]}]}], 'analyses': [{'pValue': '0.02', 'groupIds': ['OG001', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.25', 'groupIds': ['OG000', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'baseline and 96 weeks', 'description': '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).', 'unitOfMeasure': 'units on a scale', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Number of participants analyzed reflects the number of participants with baseline and 96 week liver biopsies.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Improvement in Liver Fibrosis Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '50', 'groupId': 'OG000'}, {'value': '50', 'groupId': 'OG001'}, {'value': '47', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Metformin, 500 mg, twice daily'}, {'id': 'OG001', 'title': 'Vitamin E', 'description': 'Vitamin E, 400 IU, twice daily'}, {'id': 'OG002', 'title': 'Placebo', 'description': 'Matching placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '22', 'groupId': 'OG000'}, {'value': '18', 'groupId': 'OG001'}, {'value': '19', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.71', 'groupIds': ['OG001', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.72', 'groupIds': ['OG000', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'NUMBER', 'timeFrame': 'baseline and 96 weeks', 'description': '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.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Number of participants analyzed reflects the number of participants with baseline and 96 week liver biopsies.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Improvement in Steatosis Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '50', 'groupId': 'OG000'}, {'value': '50', 'groupId': 'OG001'}, {'value': '47', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Metformin, 500 mg, twice daily'}, {'id': 'OG001', 'title': 'Vitamin E', 'description': 'Vitamin E, 400 IU, twice daily'}, {'id': 'OG002', 'title': 'Placebo', 'description': 'Matching placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '26', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}, {'value': '19', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.18', 'groupIds': ['OG001', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.25', 'groupIds': ['OG000', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'NUMBER', 'timeFrame': 'baseline and 96 weeks', 'description': '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.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Number of participants analyzed reflects the number of participants with baseline and 96 week liver biopsies.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Improvement in Lobular Inflammation Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '50', 'groupId': 'OG000'}, {'value': '50', 'groupId': 'OG001'}, {'value': '47', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Metformin, 500 mg, twice daily'}, {'id': 'OG001', 'title': 'Vitamin E', 'description': 'Vitamin E, 400 IU, twice daily'}, {'id': 'OG002', 'title': 'Placebo', 'description': 'Matching placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '23', 'groupId': 'OG000'}, {'value': '22', 'groupId': 'OG001'}, {'value': '20', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.89', 'groupIds': ['OG001', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.73', 'groupIds': ['OG000', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'NUMBER', 'timeFrame': 'baseline and 96 weeks', 'description': '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.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Number of participants analyzed reflects the number of participants with baseline and 96 week liver biopsies.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Improvement in Ballooning Degradation Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '50', 'groupId': 'OG000'}, {'value': '50', 'groupId': 'OG001'}, {'value': '47', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Metformin, 500 mg, twice daily'}, {'id': 'OG001', 'title': 'Vitamin E', 'description': 'Vitamin E, 400 IU, twice daily'}, {'id': 'OG002', 'title': 'Placebo', 'description': 'Matching placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '22', 'groupId': 'OG000'}, {'value': '22', 'groupId': 'OG001'}, {'value': '10', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.02', 'groupIds': ['OG001', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.02', 'groupIds': ['OG000', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'NUMBER', 'timeFrame': 'baseline and 96 weeks', 'description': '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.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Number of participants analyzed reflects the number of participants with baseline and 96 week liver biopsies.'}, {'type': 'SECONDARY', 'title': 'Change in Body Mass Index', 'denoms': [{'units': 'Participants', 'counts': [{'value': '51', 'groupId': 'OG000'}, {'value': '50', 'groupId': 'OG001'}, {'value': '49', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Metformin, 500 mg, twice daily'}, {'id': 'OG001', 'title': 'Vitamin E', 'description': 'Vitamin E, 400 IU, twice daily'}, {'id': 'OG002', 'title': 'Placebo', 'description': 'Matching placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '1.3', 'groupId': 'OG000', 'lowerLimit': '0.6', 'upperLimit': '2.0'}, {'value': '2.1', 'groupId': 'OG001', 'lowerLimit': '1.2', 'upperLimit': '3.0'}, {'value': '1.9', 'groupId': 'OG002', 'lowerLimit': '1.1', 'upperLimit': '2.7'}]}]}], 'analyses': [{'pValue': '0.77', 'groupIds': ['OG001', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.25', 'groupIds': ['OG000', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'baseline and 96 weeks', 'unitOfMeasure': 'kg/m-squared', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Serum Vitamin E Levels', 'denoms': [{'units': 'Participants', 'counts': [{'value': '51', 'groupId': 'OG000'}, {'value': '50', 'groupId': 'OG001'}, {'value': '49', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Metformin, 500 mg, twice daily'}, {'id': 'OG001', 'title': 'Vitamin E', 'description': 'Vitamin E, 400 IU, twice daily'}, {'id': 'OG002', 'title': 'Placebo', 'description': 'Matching placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.5', 'groupId': 'OG000', 'lowerLimit': '-1.1', 'upperLimit': '0.2'}, {'value': '9.4', 'groupId': 'OG001', 'lowerLimit': '6.2', 'upperLimit': '12.6'}, {'value': '-0.9', 'groupId': 'OG002', 'lowerLimit': '-2.1', 'upperLimit': '0.4'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG001', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.44', 'groupIds': ['OG000', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'baseline and 96 weeks', 'description': 'Change in alpha-Tocopherol', 'unitOfMeasure': 'mg/L', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Quality of Life (QOL) Scores- Physical Health', 'denoms': [{'units': 'Participants', 'counts': [{'value': '51', 'groupId': 'OG000'}, {'value': '50', 'groupId': 'OG001'}, {'value': '49', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Metformin, 500 mg, twice daily'}, {'id': 'OG001', 'title': 'Vitamin E', 'description': 'Vitamin E, 400 IU, twice daily'}, {'id': 'OG002', 'title': 'Placebo', 'description': 'Matching placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '5.4', 'groupId': 'OG000', 'lowerLimit': '0.8', 'upperLimit': '10.0'}, {'value': '7.6', 'groupId': 'OG001', 'lowerLimit': '2.7', 'upperLimit': '12.5'}, {'value': '5.4', 'groupId': 'OG002', 'lowerLimit': '-0.7', 'upperLimit': '11.5'}]}]}], 'analyses': [{'pValue': '0.08', 'groupIds': ['OG001', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.63', 'groupIds': ['OG000', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'baseline and 96 weeks', 'description': '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.', 'unitOfMeasure': 'units on a scale', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in QOL- Psychosocial Health', 'denoms': [{'units': 'Participants', 'counts': [{'value': '51', 'groupId': 'OG000'}, {'value': '50', 'groupId': 'OG001'}, {'value': '47', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Metformin, 500 mg, twice daily'}, {'id': 'OG001', 'title': 'Vitamin E', 'description': 'Vitamin E, 400 IU, twice daily'}, {'id': 'OG002', 'title': 'Placebo', 'description': 'Matching placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '4.0', 'groupId': 'OG000', 'lowerLimit': '-0.4', 'upperLimit': '8.4'}, {'value': '6.0', 'groupId': 'OG001', 'lowerLimit': '1.4', 'upperLimit': '10.6'}, {'value': '5.6', 'groupId': 'OG002', 'lowerLimit': '0.0', 'upperLimit': '11.2'}]}]}], 'analyses': [{'pValue': '0.15', 'groupIds': ['OG001', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.96', 'groupIds': ['OG000', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'baseline and 96 weeks', 'description': '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.', 'unitOfMeasure': 'units on a scale', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Metformin', 'description': 'Metformin, 500 mg, twice daily'}, {'id': 'FG001', 'title': 'Vitamin E', 'description': 'Vitamin E, 400 IU, twice daily'}, {'id': 'FG002', 'title': 'Placebo', 'description': 'Matching placebo'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '57'}, {'groupId': 'FG001', 'numSubjects': '58'}, {'groupId': 'FG002', 'numSubjects': '58'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '51'}, {'groupId': 'FG001', 'numSubjects': '50'}, {'groupId': 'FG002', 'numSubjects': '49'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '8'}, {'groupId': 'FG002', 'numSubjects': '9'}]}]}], 'recruitmentDetails': 'Between September 2005 and September 2007, 173 children were enrolled into TONIC at 10 clinical centers in the United States.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '57', 'groupId': 'BG000'}, {'value': '58', 'groupId': 'BG001'}, {'value': '58', 'groupId': 'BG002'}, {'value': '173', 'groupId': 'BG003'}]}], 'groups': [{'id': 'BG000', 'title': 'Metformin', 'description': 'Metformin, 500 mg, twice daily'}, {'id': 'BG001', 'title': 'Vitamin E', 'description': 'Vitamin E, 400 IU, twice daily'}, {'id': 'BG002', 'title': 'Placebo', 'description': 'Matching placebo'}, {'id': 'BG003', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age Continuous', 'classes': [{'categories': [{'measurements': [{'value': '13.1', 'spread': '2.4', 'groupId': 'BG000'}, {'value': '13.4', 'spread': '2.3', 'groupId': 'BG001'}, {'value': '12.9', 'spread': '2.6', 'groupId': 'BG002'}, {'value': '13.1', 'spread': '2.4', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '12', 'groupId': 'BG002'}, {'value': '33', 'groupId': 'BG003'}]}, {'title': 'Male', 'measurements': [{'value': '47', 'groupId': 'BG000'}, {'value': '47', 'groupId': 'BG001'}, {'value': '46', 'groupId': 'BG002'}, {'value': '140', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '57', 'groupId': 'BG000'}, {'value': '58', 'groupId': 'BG001'}, {'value': '58', 'groupId': 'BG002'}, {'value': '173', 'groupId': 'BG003'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'NAFLD activity score', 'classes': [{'categories': [{'measurements': [{'value': '4.5', 'spread': '1.2', 'groupId': 'BG000'}, {'value': '4.8', 'spread': '1.6', 'groupId': 'BG001'}, {'value': '4.6', 'spread': '1.3', 'groupId': 'BG002'}, {'value': '4.6', 'spread': '1.4', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'description': 'Total nonalcoholic fatty liver disease (NAFLD) activity was assessed on a scale of 0 to 8, with higher scores indicating more severe disease; the components of this measure include steatosis (assessed on a scale of 0 to 3), lobular inflammation (assessed on a scale of 0 to 3), and hepatocellular ballooning (assessed on a scale of 0 to 2).', 'unitOfMeasure': 'scores on a scale', 'dispersionType': 'STANDARD_DEVIATION'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 173}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2005-09'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2012-08', 'completionDateStruct': {'date': '2010-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2012-08-27', 'studyFirstSubmitDate': '2003-07-01', 'resultsFirstSubmitDate': '2012-06-26', 'studyFirstSubmitQcDate': '2003-07-02', 'lastUpdatePostDateStruct': {'date': '2012-09-27', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2012-08-27', 'studyFirstPostDateStruct': {'date': '2003-07-03', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2012-09-27', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2009-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'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', 'description': '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.'}], 'secondaryOutcomes': [{'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', 'description': '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).'}, {'measure': 'Number of Participants With Improvement in Liver Fibrosis Score', 'timeFrame': 'baseline and 96 weeks', 'description': '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.'}, {'measure': 'Number of Participants With Improvement in Steatosis Score', 'timeFrame': 'baseline and 96 weeks', 'description': '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.'}, {'measure': 'Number of Participants With Improvement in Lobular Inflammation Score', 'timeFrame': 'baseline and 96 weeks', 'description': '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.'}, {'measure': 'Number of Participants With Improvement in Ballooning Degradation Score', 'timeFrame': 'baseline and 96 weeks', 'description': '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.'}, {'measure': 'Change in Body Mass Index', 'timeFrame': 'baseline and 96 weeks'}, {'measure': 'Change in Serum Vitamin E Levels', 'timeFrame': 'baseline and 96 weeks', 'description': 'Change in alpha-Tocopherol'}, {'measure': 'Change in Quality of Life (QOL) Scores- Physical Health', 'timeFrame': 'baseline and 96 weeks', 'description': '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.'}, {'measure': 'Change in QOL- Psychosocial Health', 'timeFrame': 'baseline and 96 weeks', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Non alcoholic fatty liver disease'], 'conditions': ['Fatty Liver']}, 'referencesModule': {'references': [{'pmid': '25714579', 'type': 'DERIVED', '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.'}, {'pmid': '22338037', 'type': 'DERIVED', '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.'}, {'pmid': '21521847', 'type': 'DERIVED', '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.'}, {'pmid': '19761871', 'type': 'DERIVED', '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.'}], 'seeAlsoLinks': [{'url': 'http://www.niddk.nih.gov/', 'label': 'National Institute of Diabetes and Digestive and Kidney Diseases'}]}, 'descriptionModule': {'briefSummary': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '17 Years', 'minimumAge': '8 Years', 'healthyVolunteers': False, 'eligibilityCriteria': '* Age 8-17 years at first screening visit\n* Histologic evidence of Nonalcoholic Fatty Liver Disease (NAFLD) - biopsy cannot be older than 6 months as of randomization\n* 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\n* Consent'}, 'identificationModule': {'nctId': 'NCT00063635', 'acronym': 'TONIC', 'briefTitle': 'Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)', 'organization': {'class': 'NIH', 'fullName': 'National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)'}, 'officialTitle': 'Clinical Research Network in Nonalcoholic Steatohepatitis: Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)', 'orgStudyIdInfo': {'id': 'NASH - PEDIATRICS (IND)'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': '1', 'description': 'Metformin, 500 mg, twice daily', 'interventionNames': ['Drug: Metformin']}, {'type': 'ACTIVE_COMPARATOR', 'label': '2', 'description': 'Vitamin E, 400 IU, twice daily', 'interventionNames': ['Dietary Supplement: Vitamin E']}, {'type': 'PLACEBO_COMPARATOR', 'label': '3', 'description': 'Matching placebo', 'interventionNames': ['Drug: Matching placebo']}], 'interventions': [{'name': 'Metformin', 'type': 'DRUG', 'description': '500 mg, twice daily', 'armGroupLabels': ['1']}, {'name': 'Vitamin E', 'type': 'DIETARY_SUPPLEMENT', 'otherNames': ['Nature Made'], 'description': '400 IU, twice daily', 'armGroupLabels': ['2']}, {'name': 'Matching placebo', 'type': 'DRUG', 'description': 'Twice daily', 'armGroupLabels': ['3']}]}, 'contactsLocationsModule': {'locations': [{'zip': '92103', 'city': 'San Diego', 'state': 'California', 'country': 'United States', 'facility': 'University of California, San Diego', 'geoPoint': {'lat': 32.71571, 'lon': -117.16472}}, {'zip': '94143', 'city': 'San Francisco', 'state': 'California', 'country': 'United States', 'facility': 'University of California, San Francisco', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'zip': '20010', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'country': 'United States', 'facility': "Children's National Medical Center", 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}, {'zip': '46202', 'city': 'Indianapolis', 'state': 'Indiana', 'country': 'United States', 'facility': 'Indiana University', 'geoPoint': {'lat': 39.76838, 'lon': -86.15804}}, {'zip': '21205', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'Johns Hopkins University', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '63110', 'city': 'St Louis', 'state': 'Missouri', 'country': 'United States', 'facility': 'St. Louis University', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}, {'zip': '44109', 'city': 'Cleveland', 'state': 'Ohio', 'country': 'United States', 'facility': 'Case Western Reserve University', 'geoPoint': {'lat': 41.4995, 'lon': -81.69541}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': "Texas Children's Hospital", 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '23298', 'city': 'Richmond', 'state': 'Virginia', 'country': 'United States', 'facility': 'Virginia Commonwealth University', 'geoPoint': {'lat': 37.55376, 'lon': -77.46026}}, {'zip': '98195', 'city': 'Seattle', 'state': 'Washington', 'country': 'United States', 'facility': 'University of Washington', 'geoPoint': {'lat': 47.60621, 'lon': -122.33207}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)', 'class': 'NIH'}, 'responsibleParty': {'type': 'SPONSOR'}}}}