Ignite Creation Date:
2025-12-24 @ 10:12 PM
Ignite Modification Date:
2026-01-01 @ 7:25 PM
Study NCT ID:
NCT03717935
Status:
COMPLETED
Last Update Posted:
2025-03-24
First Post:
2018-06-15
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D011085', 'term': 'Polycystic Ovary Syndrome'}, {'id': 'D009765', 'term': 'Obesity'}, {'id': 'D005234', 'term': 'Fatty Liver'}], 'ancestors': [{'id': 'D010048', 'term': 'Ovarian Cysts'}, {'id': 'D003560', 'term': 'Cysts'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D010049', 'term': 'Ovarian Diseases'}, {'id': 'D000291', 'term': 'Adnexal Diseases'}, {'id': 'D005831', 'term': 'Genital Diseases, Female'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D006058', 'term': 'Gonadal Disorders'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D050177', 'term': 'Overweight'}, {'id': 'D044343', 'term': 'Overnutrition'}, {'id': 'D009748', 'term': 'Nutrition Disorders'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D001835', 'term': 'Body Weight'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000601', 'term': 'Amino Acids, Essential'}, {'id': 'D018846', 'term': 'Excitatory Amino Acids'}], 'ancestors': [{'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'melanie.green@childrenscolorado.org', 'phone': '720-777-5743', 'title': 'Melanie Cree-Green, PI', 'organization': 'University of Colorado'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': '12 weeks', 'eventGroups': [{'id': 'EG000', 'title': 'All Participants: Essential Amino Acid (EAA) Supplement vs Placebo', 'description': 'All participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo.', 'otherNumAtRisk': 27, 'deathsNumAtRisk': 27, 'otherNumAffected': 0, 'seriousNumAtRisk': 27, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Hepatic Fat Fraction', 'denoms': [{'units': 'Participants', 'counts': [{'value': '21', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Essential Amino Acid (EAA) Supplement vs Placebo', 'description': 'Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo.\n\nResults reported are measured after completing each phase of the study placebo vs EAA'}], 'classes': [{'title': 'After 4 weeks of Placebo', 'categories': [{'measurements': [{'value': '8', 'groupId': 'OG000', 'lowerLimit': '4.1', 'upperLimit': '15.9'}]}]}, {'title': 'After 4 weeks of EAA', 'categories': [{'measurements': [{'value': '7.3', 'groupId': 'OG000', 'lowerLimit': '3.9', 'upperLimit': '16'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '4 weeks after completing the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Hepatic Fat Fraction measured after completing placebo and amino acid therapy measured with MRI, and calculated via the Dixon method as the proton density hepatic fat fraction, which ranges from 0-75%. Greater than 5% is considered extra fat', 'unitOfMeasure': 'percent hepatic fat', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'adolescent girls with PCOS'}, {'type': 'SECONDARY', 'title': 'Rate of De Novo Lipogenesis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Essential Amino Acid (EAA) Supplement vs Placebo', 'description': 'Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo.\n\nResults reported are measured after completing each phase of the study placebo vs EAA'}], 'classes': [{'title': 'After 4 weeks of Placebo', 'categories': [{'measurements': [{'value': '9.60', 'spread': '6.10', 'groupId': 'OG000'}]}]}, {'title': 'After 4 weeks of EAAs', 'categories': [{'measurements': [{'value': '6.55', 'spread': '5.52', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'The rate of overnight de novo lipogenesis will be measured utilizing stable isotope methods with deuterated water, and expressed as the rate of newly synthesized lipids in the serum triglyceride fraction measured after 4 weeks of placebo and after 4 weeks of EAA intervention.', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'We were only able to obtain results for this outcome for 19 participants in the study.'}, {'type': 'SECONDARY', 'title': 'Evaluation of Mitochondrial Function', 'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Essential Amino Acid (EAA) Supplement vs Placebo', 'description': 'Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo.\n\nResults reported are measured after completing each phase of the study placebo vs EAA'}], 'classes': [{'title': 'After 4 weeks of Placebo', 'categories': [{'measurements': [{'value': '82.4', 'spread': '2.5', 'groupId': 'OG000'}]}]}, {'title': 'After 4 weeks of EAAs', 'categories': [{'measurements': [{'value': '82.5', 'spread': '2.8', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Mitochondrial function will be assessed via change in direct hepatic carbon flux in newly synthesized triglycerides (TGs) using an oral sugar tolerance test with an oral UC13 glycerol tracer after each intervention. Data from 180 minutes post-tracer drink is shown below. A higher direct percent means less indirect futile cycling through the TCA cycle.', 'unitOfMeasure': 'percent direct TG synthesis', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Hepatic Phosphate Profile After EAA and Placebo Supplement', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Essential Amino Acid (EAA) Supplement vs Placebo', 'description': 'Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo.\n\nResults reported are measured after completing each phase of the study placebo vs EAA'}], 'classes': [{'title': 'PDE/TP after EAA', 'categories': [{'measurements': [{'value': '0.19670949', 'spread': '0.049409797', 'groupId': 'OG000'}]}]}, {'title': 'PDE/TP after Placebo', 'categories': [{'measurements': [{'value': '0.186460069', 'spread': '0.034108394', 'groupId': 'OG000'}]}]}, {'title': 'PME/TP after EAA', 'categories': [{'measurements': [{'value': '0.073640887', 'spread': '0.036231645', 'groupId': 'OG000'}]}]}, {'title': 'PME/TP after Placebo', 'categories': [{'measurements': [{'value': '0.074795509', 'spread': '0.023577971', 'groupId': 'OG000'}]}]}, {'title': 'ATP/TP after EAA', 'categories': [{'measurements': [{'value': '0.561426026', 'spread': '0.088487664', 'groupId': 'OG000'}]}]}, {'title': 'ATP/TP after Placebo', 'categories': [{'measurements': [{'value': '0.564456782', 'spread': '0.053141701', 'groupId': 'OG000'}]}]}, {'title': 'Pi/TP after EAA', 'categories': [{'measurements': [{'value': '0.056107611', 'spread': '0.022628913', 'groupId': 'OG000'}]}]}, {'title': 'Pi/TP after Placebo', 'categories': [{'measurements': [{'value': '0.064446077', 'spread': '0.034944194', 'groupId': 'OG000'}]}]}, {'title': 'NADPH/TP after EAA', 'categories': [{'measurements': [{'value': '0.085554177', 'spread': '0.033832954', 'groupId': 'OG000'}]}]}, {'title': 'NADPH/TP after Placebo', 'categories': [{'measurements': [{'value': '0.069352473', 'spread': '0.035960915', 'groupId': 'OG000'}]}]}, {'title': 'UDPG/TP after EAA', 'categories': [{'measurements': [{'value': '0.02656181', 'spread': '0.017694541', 'groupId': 'OG000'}]}]}, {'title': 'UDPG/TP after Placebo', 'categories': [{'measurements': [{'value': '0.040489089', 'spread': '0.01814369', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'hepatic phosphate profile via 31 Phosphorus MR spectroscopy after each intervention\n\nHepatic phosphate relative concentrations will be measured with 31 phosphorus magnetic resonance spectroscopy after each intervention. The Total phosphate (TP) concentration will be reported after each intervention and the ratio of the following phosphate metabolites will be reported over the total phosphate concentration: Phosphodiesterase (PDE), phosphomonoester (PME), Adenosine triphosphate (ATP), Inorganic Phosphate (Pi),Nicotinamide adenine dinucleotide phosphate (NADPH), Uridine diphosphate glucose (UDPG)', 'unitOfMeasure': 'Ratio over Total Phosphate Concentration', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'We were only able to analyze 18 participants p-31 spectroscopy due to the quality of the spectra.'}, {'type': 'SECONDARY', 'title': 'Whole Body Insulin Sensitivity', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Essential Amino Acid (EAA) Supplement vs Placebo', 'description': 'Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo.\n\nResults reported are measured after completing each phase of the study placebo vs EAA'}], 'classes': [{'title': 'After 4 weeks of Placebo', 'categories': [{'measurements': [{'value': '0.00026', 'groupId': 'OG000', 'lowerLimit': '0.0002', 'upperLimit': '0.00046'}]}]}, {'title': 'After 4 weeks of EAA', 'categories': [{'measurements': [{'value': '0.00025', 'groupId': 'OG000', 'lowerLimit': '0.00021', 'upperLimit': '0.00043'}]}]}], 'paramType': 'MEAN', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Participants will undergo a 75 gram oral glucose tolerance test, and whole body insulin sensitivity will be expressed as Si, calculated via the oral minimal model using 4 hour glucose and insulin data during the OGTT after each phase of the study (placebo vs EAA).', 'unitOfMeasure': 'dl/kg/min per microU/ml', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Only 20 participants analyzed because the OMM model cannot be run if we have missing insulin or glucose values during the oral sugar tolerance test.'}, {'type': 'SECONDARY', 'title': 'Change in Adipose Insulin Sensitivity', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Essential Amino Acid (EAA) Supplement vs Placebo', 'description': 'Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo.'}], 'classes': [{'title': '4 weeks of Placebo', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '91.15', 'spread': '3.48', 'groupId': 'OG000'}]}]}, {'title': '4 weeks of EAAs', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '91.11', 'spread': '4.18', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Change from baseline of adipose insulin sensitivity will be calculated as the percent suppression of free fatty acids (FFAs) during the oral glucose tolerance test.', 'unitOfMeasure': 'percent suppression FFAs', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'This measure was completed by 22 participants in the placebo phase of the study and 20 in the EAA phase of the study'}, {'type': 'SECONDARY', 'title': 'Sleep Duration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '21', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Essential Amino Acid (EAA) Supplement vs Placebo', 'description': 'Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo.\n\nResults reported are measured after completing each phase of the study placebo vs EAA'}], 'classes': [{'title': 'After 4 weeks of placebo', 'categories': [{'measurements': [{'value': '390', 'spread': '64', 'groupId': 'OG000'}]}]}, {'title': 'After 4 weeks of EAA', 'categories': [{'measurements': [{'value': '340.7', 'spread': '95.5', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Sleep duration will be assessed completing placebo and essential amino acid therapy using home actigraphy. Change in sleep duration reported in minutes.', 'unitOfMeasure': 'minutes', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Out of these 3 participants 2 did not complete their EAA phase for this measurement, so results reported for EAA only include 21 participants.'}, {'type': 'SECONDARY', 'title': 'Apnea Hypopnea Index (AHI)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '21', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Essential Amino Acid (EAA) Supplement vs Placebo', 'description': 'Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo.\n\nResults reported are measured after completing each phase of the study placebo vs EAA'}], 'classes': [{'title': 'After 4 weeks of Placebo', 'categories': [{'measurements': [{'value': '14.99', 'spread': '7.00', 'groupId': 'OG000'}]}]}, {'title': 'After 4 weeks of EAA', 'categories': [{'measurements': [{'value': '17.04', 'spread': '8.44', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Apnea Hypopnea Index (AHI) will be measured using WatchPAT after each intervention. In children and adolescents the scale that will be used is AHI\\>5 is considered mild sleep apnea. The higher the AHI, indicates more severe sleep apnea.\n\nThe AHI is the number of times you have apnea or hypopnea during one night, divided by the hours of sleep.\n\nNormal sleep: An AHI of fewer than five events, on average, per hour Mild sleep apnea: An AHI of five to 14 events per hour Moderate sleep apnea: An AHI of 15 to 29 events per hour Severe sleep apnea: An AHI of 30 or more events per hour', 'unitOfMeasure': 'events per hour', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Out of these 3 participants 2 did not complete their EAA phase for this measurement, so results reported for EAA only include 21 participants.'}, {'type': 'SECONDARY', 'title': 'Amino Acid Metabolomics: Alanine, Glutamate, Leucine, Valine Levels After 4 Weeks of Placebo and 4 Weeks of EAAs', 'denoms': [{'units': 'Participants', 'counts': [{'value': '21', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Essential Amino Acid (EAA) Supplement vs Placebo', 'description': 'Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo.'}], 'classes': [{'title': 'Alanine after Placebo', 'categories': [{'measurements': [{'value': '420', 'spread': '120', 'groupId': 'OG000'}]}]}, {'title': 'Glutamate after Placebo', 'categories': [{'measurements': [{'value': '49', 'spread': '20', 'groupId': 'OG000'}]}]}, {'title': 'Leucine after Placebo', 'categories': [{'measurements': [{'value': '91', 'spread': '16', 'groupId': 'OG000'}]}]}, {'title': 'Valine after Placebo', 'categories': [{'measurements': [{'value': '303', 'spread': '36', 'groupId': 'OG000'}]}]}, {'title': 'Alanine after EAAs', 'categories': [{'measurements': [{'value': '385', 'spread': '116', 'groupId': 'OG000'}]}]}, {'title': 'Glutamate after EAAs', 'categories': [{'measurements': [{'value': '54', 'spread': '21', 'groupId': 'OG000'}]}]}, {'title': 'Leucine after EAAs', 'categories': [{'measurements': [{'value': '88', 'spread': '20', 'groupId': 'OG000'}]}]}, {'title': 'Valine after EAAs', 'categories': [{'measurements': [{'value': '284', 'spread': '46', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Targeted amino acid metabolomics will be performed after each intervention and the levels of these 4 amino acids will be reported after each intervention.', 'unitOfMeasure': 'micro molar', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Lipid Metabolomics: 16n1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '21', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Essential Amino Acid (EAA) Supplement vs Placebo', 'description': 'Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo.'}], 'classes': [{'title': 'After 4 weeks of Placebo', 'categories': [{'measurements': [{'value': '87', 'spread': '45', 'groupId': 'OG000'}]}]}, {'title': 'After 4 weeks of EAAs', 'categories': [{'measurements': [{'value': '88', 'spread': '32', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Targeted lipid metabolomics will be performed after each intervention to measure 16n1 lipids after completing 4 weeks of essential amino acid therapy and 4 weeks of placebo.', 'unitOfMeasure': 'micro molar', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Bile Acid Metabolomics: Sphingosine-1-phospate After 4 Weeks of Placebo and 4 Weeks of EAAs', 'denoms': [{'units': 'Participants', 'counts': [{'value': '21', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Essential Amino Acid (EAA) Supplement vs Placebo', 'description': 'Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo.'}], 'classes': [{'title': 'After 4 weeks Placebo', 'categories': [{'measurements': [{'value': '1334', 'spread': '194', 'groupId': 'OG000'}]}]}, {'title': 'After 4 weeks EAAs', 'categories': [{'measurements': [{'value': '1294', 'spread': '281', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Targeted bile acid metabolomics will be performed after each intervention to measure levels of sphingosine-1-phospate', 'unitOfMeasure': 'micro molar', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Essential Amino Acid (EAA) Supplement Followed by Placebo', 'description': 'Participants completed: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks washout period and then 4 weeks of Placebo- 15g 2/day.'}, {'id': 'FG001', 'title': 'Placebo Followed by Essential Amino Acid (EAA) Supplement', 'description': 'Participants completed: 4 weeks of Placebo- 15g 2/day followed by 4 weeks washout period and then 4 weeks of Essential Amino Acid Supplement- 15g 2/day.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '11'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '11'}, {'groupId': 'FG001', 'numSubjects': '10'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '2'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '2'}]}]}], 'preAssignmentDetails': 'This was a crossover study. There were a total of 27 participants enrolled in the study. Four participants were never randomized: 3 screen failed and 1 of withdrew. Two participants withdrew after completing the placebo phase of the study'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '27', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'All Study Participants: Essential Amino Acid (EAA) Supplement vs Placebo', 'description': 'All study participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo between all participants.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '15.67', 'spread': '1.44', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '27', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '16', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '11', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '27', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2020-06-09', 'size': 3274256, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2024-04-11T16:21', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Investigational drug pharmacy will performed randomization and dispense the EAA or placebo.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 27}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-10-08', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-03', 'completionDateStruct': {'date': '2022-01-14', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-03-04', 'studyFirstSubmitDate': '2018-06-15', 'resultsFirstSubmitDate': '2024-04-15', 'studyFirstSubmitQcDate': '2018-10-22', 'lastUpdatePostDateStruct': {'date': '2025-03-24', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2025-03-04', 'studyFirstPostDateStruct': {'date': '2018-10-24', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2025-03-24', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-01-14', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Hepatic Fat Fraction', 'timeFrame': '4 weeks after completing the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Hepatic Fat Fraction measured after completing placebo and amino acid therapy measured with MRI, and calculated via the Dixon method as the proton density hepatic fat fraction, which ranges from 0-75%. Greater than 5% is considered extra fat'}], 'secondaryOutcomes': [{'measure': 'Rate of De Novo Lipogenesis', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'The rate of overnight de novo lipogenesis will be measured utilizing stable isotope methods with deuterated water, and expressed as the rate of newly synthesized lipids in the serum triglyceride fraction measured after 4 weeks of placebo and after 4 weeks of EAA intervention.'}, {'measure': 'Evaluation of Mitochondrial Function', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Mitochondrial function will be assessed via change in direct hepatic carbon flux in newly synthesized triglycerides (TGs) using an oral sugar tolerance test with an oral UC13 glycerol tracer after each intervention. Data from 180 minutes post-tracer drink is shown below. A higher direct percent means less indirect futile cycling through the TCA cycle.'}, {'measure': 'Hepatic Phosphate Profile After EAA and Placebo Supplement', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'hepatic phosphate profile via 31 Phosphorus MR spectroscopy after each intervention\n\nHepatic phosphate relative concentrations will be measured with 31 phosphorus magnetic resonance spectroscopy after each intervention. The Total phosphate (TP) concentration will be reported after each intervention and the ratio of the following phosphate metabolites will be reported over the total phosphate concentration: Phosphodiesterase (PDE), phosphomonoester (PME), Adenosine triphosphate (ATP), Inorganic Phosphate (Pi),Nicotinamide adenine dinucleotide phosphate (NADPH), Uridine diphosphate glucose (UDPG)'}, {'measure': 'Whole Body Insulin Sensitivity', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Participants will undergo a 75 gram oral glucose tolerance test, and whole body insulin sensitivity will be expressed as Si, calculated via the oral minimal model using 4 hour glucose and insulin data during the OGTT after each phase of the study (placebo vs EAA).'}, {'measure': 'Change in Adipose Insulin Sensitivity', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Change from baseline of adipose insulin sensitivity will be calculated as the percent suppression of free fatty acids (FFAs) during the oral glucose tolerance test.'}, {'measure': 'Sleep Duration', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Sleep duration will be assessed completing placebo and essential amino acid therapy using home actigraphy. Change in sleep duration reported in minutes.'}, {'measure': 'Apnea Hypopnea Index (AHI)', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Apnea Hypopnea Index (AHI) will be measured using WatchPAT after each intervention. In children and adolescents the scale that will be used is AHI\\>5 is considered mild sleep apnea. The higher the AHI, indicates more severe sleep apnea.\n\nThe AHI is the number of times you have apnea or hypopnea during one night, divided by the hours of sleep.\n\nNormal sleep: An AHI of fewer than five events, on average, per hour Mild sleep apnea: An AHI of five to 14 events per hour Moderate sleep apnea: An AHI of 15 to 29 events per hour Severe sleep apnea: An AHI of 30 or more events per hour'}, {'measure': 'Amino Acid Metabolomics: Alanine, Glutamate, Leucine, Valine Levels After 4 Weeks of Placebo and 4 Weeks of EAAs', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Targeted amino acid metabolomics will be performed after each intervention and the levels of these 4 amino acids will be reported after each intervention.'}, {'measure': 'Lipid Metabolomics: 16n1', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Targeted lipid metabolomics will be performed after each intervention to measure 16n1 lipids after completing 4 weeks of essential amino acid therapy and 4 weeks of placebo.'}, {'measure': 'Bile Acid Metabolomics: Sphingosine-1-phospate After 4 Weeks of Placebo and 4 Weeks of EAAs', 'timeFrame': '4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)', 'description': 'Targeted bile acid metabolomics will be performed after each intervention to measure levels of sphingosine-1-phospate'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['hepatic de novo lipogenesis'], 'conditions': ['Polycystic Ovarian Syndrome', 'Obesity', 'Hepatic Steatosis']}, 'descriptionModule': {'briefSummary': 'The Investigators will measure hepatic glucose and fat metabolism in obese girls with Polycystic Ovarian Syndrome (PCOS) and hepatic steatosis (HS) after taking 4 weeks of an essential amino acid (EAA) supplement or placebo and test whether the EAA supplement can improve hepatic glucose metabolism in these girls.', 'detailedDescription': 'Girls with Polycystic Ovarian Syndrome (PCOS) and hepatic steatosis (HS) will complete a 12 week double-blinded placebo controlled cross-over study with 4 weeks each of an essential amino acid (EAA) supplement and placebo, and will complete metabolic studies after each intervention. There will be a 4 week wash out period in-between. The metabolic tests after each intervention (EAA/placebo) will include an oral sugar tolerance test (OSTT) and an oral U-C13 glycerol tracer that is paired with Nuclear Magnetic Resonance (NMR) isotopomer analysis of serum samples to describe flux through the hepatic pentose phosphate pathway, tricarboxylic acid (TCA) cycle and fatty acid synthesis pathways in girls with PCOS and HS. Hepatic steatosis will be measured with magnetic resonance Imaging (MRI) and hepatic phosphate concentrations with magnetic resonance (MR) spectroscopy.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '21 Years', 'minimumAge': '12 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Females\n2. Ages 12-21\n3. Sedentary- less than 2 hours of moderate (jogging, swimming etc) exercise a week.\n4. BMI equal or greater than the 90th percentile for age and gender\n5. PCOS per the most stringent NIH criteria adapted for adolescents (irregular menses \\>24 months post-menarche and clinical or biochemical hypertestosteronemia)\n6. HS per FibroScan ultrasound, with CAP score of \\>225 (will be measured at screening visit)\n\nExclusion Criteria:\n\n1. Use of medications known to affect insulin sensitivity: metformin, oral glucocorticoids within 10 days, atypical antipsychotics, immunosuppressant agents, HIV medications, hormonal contraception. Dermal patch or vaginal ring contraception methods.\n2. Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study.\n3. Severe illness requiring hospitalization within 60 days\n4. Diabetes, defined as Hemoglobin A1C \\> 6.4%\n5. BMI percentile less than the 90th percentile for age and sex. Weight \\>325 lbs or \\<84 lbs.\n6. Anemia, defined as Hemoglobin \\< 11 mg/dL\n7. Diagnosed major psychiatric or developmental disorder limiting informed consent\n8. Implanted metal devices that are not compatible with MRI\n9. Use of blood pressure medications\n10. Known liver disease other than NAFLD or AST or ALT \\>125 IU/L'}, 'identificationModule': {'nctId': 'NCT03717935', 'acronym': 'ORANGE', 'briefTitle': 'Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS', 'organization': {'class': 'OTHER', 'fullName': 'University of Colorado, Denver'}, 'officialTitle': 'Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS', 'orgStudyIdInfo': {'id': '18-0803'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Essential Amino Acid (EAA) Supplement', 'description': '4 weeks: Essential Amino Acid Supplement- 15g 2/day', 'interventionNames': ['Dietary Supplement: Essential Amino Acid (EAA) Supplement', 'Other: Placebo']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': '4 weeks: Placebo- 15g 2/day', 'interventionNames': ['Dietary Supplement: Essential Amino Acid (EAA) Supplement', 'Other: Placebo']}], 'interventions': [{'name': 'Essential Amino Acid (EAA) Supplement', 'type': 'DIETARY_SUPPLEMENT', 'description': 'Powder supplement', 'armGroupLabels': ['Essential Amino Acid (EAA) Supplement', 'Placebo']}, {'name': 'Placebo', 'type': 'OTHER', 'description': 'Powder that will be similar to the essential amino acid supplement', 'armGroupLabels': ['Essential Amino Acid (EAA) Supplement', 'Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'facility': 'University of Colorado, Anschutz Medical Campus', 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}], 'overallOfficials': [{'name': 'Melanie Cree-Green, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Department of Endocrinology'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'Data will only be shared with IRB approved personnel.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Colorado, Denver', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}