Ignite Creation Date:
2025-12-25 @ 3:14 AM
Ignite Modification Date:
2025-12-26 @ 1:52 AM
Study NCT ID:
NCT00345605
Status:
COMPLETED
Last Update Posted:
2018-01-31
First Post:
2006-06-26
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Arginine and Buphenyl in Patients With Argininosuccinic Aciduria (ASA), a Urea Cycle Disorder
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D056807', 'term': 'Argininosuccinic Aciduria'}, {'id': 'D000592', 'term': 'Amino Acid Metabolism, Inborn Errors'}, {'id': 'D056806', 'term': 'Urea Cycle Disorders, Inborn'}], 'ancestors': [{'id': 'D020739', 'term': 'Brain Diseases, Metabolic, Inborn'}, {'id': 'D001928', 'term': 'Brain Diseases, Metabolic'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C075773', 'term': '4-phenylbutyric acid'}, {'id': 'D001120', 'term': 'Arginine'}], 'ancestors': [{'id': 'D024361', 'term': 'Amino Acids, Basic'}, {'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D000599', 'term': 'Amino Acids, Diamino'}, {'id': 'D000601', 'term': 'Amino Acids, Essential'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'nagamani@bcm.edu', 'title': 'Dr. Sandesh Nagamani', 'organization': 'Baylor College of Medicine'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': 'during both of the 7 day treatment phases', 'eventGroups': [{'id': 'EG000', 'title': 'High-dose Arginine Alone', 'otherNumAtRisk': 12, 'otherNumAffected': 1, 'seriousNumAtRisk': 12, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Low-dose Arginine Plus Buphenyl', 'otherNumAtRisk': 12, 'otherNumAffected': 1, 'seriousNumAtRisk': 12, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Hyperammonemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Measures of Liver Function: AST and ALT', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Low-dose Arginine Plus Buphenyl', 'description': 'Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine; a 3-day washout period; a 1-week treatment period of arginine alone.'}, {'id': 'OG001', 'title': 'High Dose Arginine Alone', 'description': 'Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of arginine alone; a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine'}], 'classes': [{'title': 'Plasma AST', 'categories': [{'measurements': [{'value': '36.2', 'spread': '10.9', 'groupId': 'OG000'}, {'value': '52', 'spread': '15.7', 'groupId': 'OG001'}]}]}, {'title': 'ALT', 'categories': [{'measurements': [{'value': '31.7', 'spread': '9.55', 'groupId': 'OG000'}, {'value': '57.86', 'spread': '17.44', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Slope', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.5', 'estimateComment': 'Assuming r=0.5 between two measurements from the same subject, 12 subjects would provide a power of 0.8 to detect a 10% reduction in primary endpoints at an alpha value of 0.05.', 'groupDescription': 'For sample size calculation, we used the means and standard deviation for PT, PTT. Assuming r=0.5 between two measurements from the same subject, 12 subjects would provide a power of 0.8 to detect a 10% reduction in primary endpoints at an alpha value of 0.05.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Measured after each 1-week treatment period', 'description': 'Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured.', 'unitOfMeasure': 'IU/L', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Argininosuccinic Acid Levels', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'High-dose Arginine Alone'}, {'id': 'OG001', 'title': 'Low-dose Arginine Plus Buphenyl'}], 'classes': [{'categories': [{'measurements': [{'value': '69', 'groupId': 'OG000', 'lowerLimit': '44', 'upperLimit': '165'}, {'value': '53', 'groupId': 'OG001', 'lowerLimit': '29', 'upperLimit': '118'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Measured after each 1-week treatment period', 'unitOfMeasure': 'micromole/l', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Arginine Levels', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'High-dose Arginine Alone'}, {'id': 'OG001', 'title': 'Low-dose Arginine Plus Buphenyl'}], 'classes': [{'categories': [{'measurements': [{'value': '129', 'groupId': 'OG000', 'lowerLimit': '83', 'upperLimit': '197'}, {'value': '53', 'groupId': 'OG001', 'lowerLimit': '41', 'upperLimit': '61'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Measured after each 1-week treatment period', 'unitOfMeasure': 'micromoles/L', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Urea Production Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'High-dose Arginine Alone'}, {'id': 'OG001', 'title': 'Low-dose Arginine Plus Buphenyl'}], 'classes': [{'categories': [{'measurements': [{'value': '215', 'spread': '56', 'groupId': 'OG000'}, {'value': '97', 'spread': '35', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Measured after each 1-week treatment period', 'unitOfMeasure': 'micromoles/kg/hr', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'PRIMARY', 'title': 'Measures of Liver Function: PT and PTT', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Low-dose Arginine Plus Buphenyl', 'description': 'Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine; a 3-day washout period; a 1-week treatment period of arginine alone.'}, {'id': 'OG001', 'title': 'High Dose Arginine Alone', 'description': 'Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of arginine alone; a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine'}], 'classes': [{'title': 'PT', 'categories': [{'measurements': [{'value': '14.25', 'groupId': 'OG000', 'lowerLimit': '13.7', 'upperLimit': '14.6'}, {'value': '13.8', 'groupId': 'OG001', 'lowerLimit': '13.6', 'upperLimit': '14.37'}]}]}, {'title': 'PTT', 'categories': [{'measurements': [{'value': '30.91', 'groupId': 'OG000', 'lowerLimit': '29.55', 'upperLimit': '32.54'}, {'value': '30.98', 'groupId': 'OG001', 'lowerLimit': '29.16', 'upperLimit': '31.74'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Measured after each 1-week treatment period', 'description': 'Prothrombin time (PT) and partial thromboplastin time (PTT) were measured PT measures factors I (fibrinogen), II (prothrombin), V, VII, and X, while PTT is a performance indicator of the efficacy of the common coagulation pathways.', 'unitOfMeasure': 'seconds', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'PRIMARY', 'title': 'Measures of Liver Function: Coagulation Factors', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Low-dose Arginine Plus Buphenyl', 'description': 'Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine; a 3-day washout period; a 1-week treatment period of arginine alone.'}, {'id': 'OG001', 'title': 'High Dose Arginine Alone', 'description': 'Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of arginine alone; a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine'}], 'classes': [{'title': 'I', 'categories': [{'measurements': [{'value': '222.22', 'spread': '47.26', 'groupId': 'OG000'}, {'value': '229.77', 'spread': '62.96', 'groupId': 'OG001'}]}]}, {'title': 'IX', 'categories': [{'measurements': [{'value': '105.33', 'spread': '33.2', 'groupId': 'OG000'}, {'value': '98.36', 'spread': '21.03', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Measured after each 1-week treatment period', 'description': 'Plasma levels of coagulation factors I and IX were used as measures of hepatic synthetic function since the treatment duration was short.', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'PRIMARY', 'title': 'Measures of Liver Function: INR', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Low-dose Arginine Plus Buphenyl', 'description': 'Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine; a 3-day washout period; a 1-week treatment period of arginine alone.'}, {'id': 'OG001', 'title': 'High Dose Arginine Alone', 'description': 'Participants will undergo treatments in the following order: a 3-day washout period; a 1-week treatment period of arginine alone; a 3-day washout period; a 1-week treatment period of sodium phenylbutyrate (Buphenyl-TM) plus arginine'}], 'classes': [{'categories': [{'measurements': [{'value': '14.2', 'groupId': 'OG000', 'lowerLimit': '13.7', 'upperLimit': '14.6'}, {'value': '13.8', 'groupId': 'OG001', 'lowerLimit': '13.6', 'upperLimit': '14.3'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Measured after each 1-week treatment period', 'description': "The result (in seconds) for a prothrombin time performed on a normal individual will vary according to the type of analytical system employed. This is due to the variations between different batches of manufacturer's tissue factor used in the reagent to perform the test. The INR was devised to standardize the results. Each manufacturer assigns an ISI value (International Sensitivity Index) for any tissue factor they manufacture. The ISI value indicates how a particular batch of tissue factor compares to an international reference tissue factor. The ISI is usually between 1.0 and 2.0. The INR is the ratio of a patient's prothrombin time to a normal (control) sample, raised to the power of the ISI value for the analytical system being used.", 'unitOfMeasure': 'seconds', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'High Dose First', 'description': 'High dose arm 3 day wash-out followed by 7 days of: Arg 500 mg/kg/d or 10 g/m2 BSA Placebo instead of NaPBA interval then: Arg 100 mg/kg/d or 2 g/m2 BSA NaPBA 500 mg/kg/d or 10 g/m2 BSA'}, {'id': 'FG001', 'title': 'Low Dose First', 'description': 'low dose arm 3 day wash-out followed by 7 days of: Arg 100 mg/kg/d or 2 g/m2 BSA NaPBA 500 mg/kg/d or 10 g/m2 BSA interval then: Arg 500 mg/kg/d or 10 g/m2 BSA Placebo instead of NaPBA'}], 'periods': [{'title': 'Initial Washout', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Arm 1', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '5'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}, {'title': 'Interval', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Crossover Wash-out', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Arm 2, Opposite Treatment', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': '12 subjects with argininosuccinic aciduria were recruited at Baylor College of Medicine from May 2008 to December 2010.', 'preAssignmentDetails': 'patients were randomly assigned to one of the two arms HDA or LDA after treatment and an interval the same patients returned and received the crossover treatment LD or HDA depending.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'High-dose Arginine vs Low-dose Arginine Plus Buphenyl'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '8', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '4', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '15.4', 'spread': '7.2', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '7', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '5', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '12', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 12}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2008-02'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-10', 'completionDateStruct': {'date': '2012-11', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-01-26', 'studyFirstSubmitDate': '2006-06-26', 'resultsFirstSubmitDate': '2014-05-15', 'studyFirstSubmitQcDate': '2006-06-26', 'lastUpdatePostDateStruct': {'date': '2018-01-31', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2014-11-03', 'studyFirstPostDateStruct': {'date': '2006-06-28', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2014-11-05', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2011-05', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Measures of Liver Function: AST and ALT', 'timeFrame': 'Measured after each 1-week treatment period', 'description': 'Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured.'}, {'measure': 'Measures of Liver Function: PT and PTT', 'timeFrame': 'Measured after each 1-week treatment period', 'description': 'Prothrombin time (PT) and partial thromboplastin time (PTT) were measured PT measures factors I (fibrinogen), II (prothrombin), V, VII, and X, while PTT is a performance indicator of the efficacy of the common coagulation pathways.'}, {'measure': 'Measures of Liver Function: Coagulation Factors', 'timeFrame': 'Measured after each 1-week treatment period', 'description': 'Plasma levels of coagulation factors I and IX were used as measures of hepatic synthetic function since the treatment duration was short.'}, {'measure': 'Measures of Liver Function: INR', 'timeFrame': 'Measured after each 1-week treatment period', 'description': "The result (in seconds) for a prothrombin time performed on a normal individual will vary according to the type of analytical system employed. This is due to the variations between different batches of manufacturer's tissue factor used in the reagent to perform the test. The INR was devised to standardize the results. Each manufacturer assigns an ISI value (International Sensitivity Index) for any tissue factor they manufacture. The ISI value indicates how a particular batch of tissue factor compares to an international reference tissue factor. The ISI is usually between 1.0 and 2.0. The INR is the ratio of a patient's prothrombin time to a normal (control) sample, raised to the power of the ISI value for the analytical system being used."}], 'secondaryOutcomes': [{'measure': 'Argininosuccinic Acid Levels', 'timeFrame': 'Measured after each 1-week treatment period'}, {'measure': 'Arginine Levels', 'timeFrame': 'Measured after each 1-week treatment period'}, {'measure': 'Urea Production Rate', 'timeFrame': 'Measured after each 1-week treatment period'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Argininosuccinic Acid Lyase Deficiency', 'ASA'], 'conditions': ['Argininosuccinic Aciduria', 'Amino Acid Metabolism, Inborn Errors', 'Urea Cycle Disorders']}, 'referencesModule': {'references': [{'pmid': '12970464', 'type': 'BACKGROUND', 'citation': 'Annet L, Materne R, Danse E, Jamart J, Horsmans Y, Van Beers BE. Hepatic flow parameters measured with MR imaging and Doppler US: correlations with degree of cirrhosis and portal hypertension. Radiology. 2003 Nov;229(2):409-14. doi: 10.1148/radiol.2292021128. Epub 2003 Sep 11.'}, {'pmid': '14606100', 'type': 'BACKGROUND', 'citation': 'Lu LG, Zeng MD, Wan MB, Li CZ, Mao YM, Li JQ, Qiu DK, Cao AP, Ye J, Cai X, Chen CW, Wang JY, Wu SM, Zhu JS, Zhou XQ. Grading and staging of hepatic fibrosis, and its relationship with noninvasive diagnostic parameters. World J Gastroenterol. 2003 Nov;9(11):2574-8. doi: 10.3748/wjg.v9.i11.2574.'}, {'pmid': '14522733', 'type': 'BACKGROUND', 'citation': 'Scaglia F, Marini J, Rosenberger J, Henry J, Garlick P, Lee B, Reeds P. Differential utilization of systemic and enteral ammonia for urea synthesis in control subjects and ornithine transcarbamylase deficiency carriers. Am J Clin Nutr. 2003 Oct;78(4):749-55. doi: 10.1093/ajcn/78.4.749.'}, {'pmid': '10869432', 'type': 'BACKGROUND', 'citation': "Lee B, Yu H, Jahoor F, O'Brien W, Beaudet AL, Reeds P. In vivo urea cycle flux distinguishes and correlates with phenotypic severity in disorders of the urea cycle. Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8021-6. doi: 10.1073/pnas.140082197."}, {'pmid': '8794176', 'type': 'BACKGROUND', 'citation': 'Brusilow SW, Maestri NE. Urea cycle disorders: diagnosis, pathophysiology, and therapy. Adv Pediatr. 1996;43:127-70. No abstract available.'}]}, 'descriptionModule': {'briefSummary': 'Urea cycle disorders are inherited illnesses in which the body does not produce enough of the chemicals that remove ammonia, a byproduct of protein metabolism, from the blood stream. Elevated ammonia levels can lead to brain damage and death. Argininosuccinic aciduria (ASA) is a type of urea cycle disorder that is characterized specifically by high levels of argininosuccinic acid, a chemical involved in the urea cycle. People with ASA are at risk for serious liver damage, which may be due to the elevated levels of argininosuccinic acid. Sodium phenylbutyrate (Buphenyl-TM) is a drug that has been used to treat other types of urea cycle disorders. This study will evaluate whether Buphenyl-TM in conjunction with decreased arginine dose (in addition to a normal regimen of protein) will improve short-term liver function and decrease plasma citrulline and ASA levels in people with ASA.', 'detailedDescription': 'The cause of liver damage in people with ASA is unknown. However, because ASA is the only urea cycle disorder that is characterized by both liver damage and elevated levels of argininosuccinic acid, researchers believe that the elevated acid levels cause the liver damage. Common treatments for urea cycle disorders include a low-protein diet and arginine supplementation, which, when combined, help to decrease ammonia levels in the blood. Buphenyl-TM may aid in lowering ammonia and argininosuccinic acid levels. Although Buphenyl-TM has been FDA-approved for use in people with some types of urea cycle disorders, there is little information on the effectiveness of the drug in children with ASA. This study will evaluate whether treatment of ASA patients with Buphenyl-TM in conjunction with lowered doses of arginine improves liver function as measured by short-term assessment of synthetic activity and the use of stable isotope tracers to assess ureagenesis and nitric oxide production.\n\nInitially, participants in this double-blind, placebo-controlled, crossover study will undergo a 3-day washout period during which no Buphenyl-TM will be given. They will then be randomly assigned to one of two groups: either Buphenyl-TM (500 mg/kg/day or 10 grams/m2) and arginine (100 mg/kg/day or 2 grams/m2)), or arginine alone (500 mg/kg/day or 10 grams/m2). Participants will remain on this initial treatment arm for 1 week, at the conclusion of which an assessment of hepatic synthetic function, ureagenesis, and nitric oxide production will be performed. After this assessment, participants will undergo a second 3-day washout and then crossover to the other treatment arm for 1 week. At the end of the 1-week treatment period, a second assessment will be performed. During the washout period before each treatment period, no Buphenyl-TM will be administered, and arginine will be administered at the standard therapeutic dose of 500 mg/kg/day or 10 grams/2.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '5 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Has confirmed diagnosis of ASA by amino acid or enzyme assay\n* Has a history of adequate compliance to the diet and treatment\n* Able to take oral or G-tube medication\n* Able to perform 24 hour urine collection\n* Agrees to travel to Baylor College of Medicine\n* If female, of child bearing potential, and sexually active, agrees to use an acceptable method of birth control\n* Greater than 5 years of age\n\nExclusion Criteria:\n\n* Has a history of congestive heart failure, severe renal insufficiency, or any condition that causes sodium retention or edema\n* Currently taking Probenecid, Haloperidol, Valproate or oral corticosteroids\n* Pregnant or lactating\n* Currently being treated for an acute illness\n* Has co-morbid associations causing difficulties in the detection of hyperammonemic episodes, liver damage, or difficulties in the diet compliance\n* Has known hypersensitivity to sodium phenylbutyrate\n* Has taken any experimental medication within the last 30 days\n* Has renal insufficiency with creatinine greater than 1.5 mg/dl at screening'}, 'identificationModule': {'nctId': 'NCT00345605', 'briefTitle': 'Arginine and Buphenyl in Patients With Argininosuccinic Aciduria (ASA), a Urea Cycle Disorder', 'organization': {'class': 'OTHER', 'fullName': 'Baylor College of Medicine'}, 'officialTitle': 'A Randomized, Double-Blind, Crossover Study of Sodium Phenylbutyrate and Low-Dose Arginine Compared to High-Dose Arginine Alone on Liver Function, Ureagenesis and Subsequent Nitric Oxide Production in Patients With Argininosuccinic Aciduria', 'orgStudyIdInfo': {'id': 'RDCRN 5102'}, 'secondaryIdInfos': [{'id': 'U54HD061221', 'link': 'https://reporter.nih.gov/quickSearch/U54HD061221', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'HDA', 'description': 'High Dose Arm\n\nWash-out then 7 days of:\n\nArg 500 mg/kg/d or 10 g/m2 BSA Placebo instead of NaPBA', 'interventionNames': ['Drug: Sodium Phenylbutyrate', 'Drug: Arginine']}, {'type': 'EXPERIMENTAL', 'label': 'LDA', 'description': 'Low Dose Arm\n\nWash-out followed by 7 days of:\n\nArg 100 mg/kg/d or 2 g/m2 BSA NaPBA 500 mg/kg/d or 10 g/m2 BSA', 'interventionNames': ['Drug: Sodium Phenylbutyrate', 'Drug: Arginine']}], 'interventions': [{'name': 'Sodium Phenylbutyrate', 'type': 'DRUG', 'otherNames': ['Buphenyl-TM'], 'description': 'None will be administered during the washout period; 500 mg/kg/day or 10 grams/m2 will be administered during the first one week treatment period in addition to arginine', 'armGroupLabels': ['HDA', 'LDA']}, {'name': 'Arginine', 'type': 'DRUG', 'description': 'Standard therapeutic dose of 500 mg/kg/day or 10 grams/2 will be administered during the washout periods, during the first one week treatment period when receiving arginine plus Buphenyl, 100 mg/kg/day or 2 grams/m2 will be administered, during the second treatment week, when receiving arginine alone, 500 mg/kg/day or 10 grams/m2 will be administered', 'armGroupLabels': ['HDA', 'LDA']}]}, 'contactsLocationsModule': {'locations': [{'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'Baylor College of Medicine', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}], 'overallOfficials': [{'name': 'Brendan Lee, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Baylor College of Medicine'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Brendan Lee', 'class': 'OTHER'}, 'collaborators': [{'name': 'Office of Rare Diseases (ORD)', 'class': 'NIH'}, {'name': 'Rare Diseases Clinical Research Network', 'class': 'NETWORK'}, {'name': 'Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)', 'class': 'NIH'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'MD, PhD', 'investigatorFullName': 'Brendan Lee', 'investigatorAffiliation': 'Baylor College of Medicine'}}}}