Ignite Creation Date:
2025-12-24 @ 5:39 PM
Ignite Modification Date:
2025-12-30 @ 3:07 AM
Study NCT ID:
NCT01569568
Status:
COMPLETED
Last Update Posted:
2024-03-08
First Post:
2012-03-30
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Investigation of Brain Nitrogen in Partial Ornithine Transcarbamylase Deficiency (OTCD) Using 1 H MRS, DTI, and fMRI
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['United States']}, 'conditionBrowseModule': {'meshes': [{'id': 'D020163', 'term': 'Ornithine Carbamoyltransferase Deficiency Disease'}, {'id': 'D022124', 'term': 'Hyperammonemia'}], 'ancestors': [{'id': 'D056806', 'term': 'Urea Cycle Disorders, Inborn'}, {'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': 'D040181', 'term': 'Genetic Diseases, X-Linked'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D000592', 'term': 'Amino Acid Metabolism, Inborn Errors'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D009483', 'term': 'Neuropsychological Tests'}], 'ancestors': [{'id': 'D011581', 'term': 'Psychological Tests'}, {'id': 'D004191', 'term': 'Behavioral Disciplines and Activities'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'agropman@childrensnational.org', 'phone': '202-476-2120', 'title': 'Dr. Andrea Gropman', 'organization': "Children's National Medical Center"}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Subjects With OTCD', 'description': 'males and females ages 7-60 years with OTCD\n\nMRI scanning: 1H MRS, DTI, FMRI\n\nCognitive testing: Neuropsychological testing', 'otherNumAtRisk': 20, 'otherNumAffected': 0, 'seriousNumAtRisk': 20, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Healthy Controls', 'description': 'males and females ages 7-60 years who are healthy controls\n\nMRI scanning: 1H MRS, DTI, FMRI\n\nCognitive testing: Neuropsychological testing', 'otherNumAtRisk': 29, 'otherNumAffected': 0, 'seriousNumAtRisk': 29, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Concentration of Glutamine and Myoinositol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Subjects With OTCD', 'description': 'males and females ages 7-60 years with OTCD\n\nMRI scanning: 1H MRS, DTI, FMRI\n\nCognitive testing: Neuropsychological testing'}, {'id': 'OG001', 'title': 'Healthy Controls', 'description': 'males and females ages 7-60 years who are healthy controls\n\nMRI scanning: 1H MRS, DTI, FMRI\n\nCognitive testing: Neuropsychological testing'}], 'classes': [{'title': 'Concentration of glutamine in PWM', 'categories': [{'measurements': [{'value': '2.61', 'spread': '1.07', 'groupId': 'OG000'}, {'value': '1.66', 'spread': '0.93', 'groupId': 'OG001'}]}]}, {'title': 'Concentration of myoinositol in PWM', 'categories': [{'measurements': [{'value': '2.23', 'spread': '0.84', 'groupId': 'OG000'}, {'value': '2.69', 'spread': '0.48', 'groupId': 'OG001'}]}]}, {'title': 'Concentration of glutamine in PCGM', 'categories': [{'measurements': [{'value': '5.22', 'spread': '1.70', 'groupId': 'OG000'}, {'value': '3.62', 'spread': '0.91', 'groupId': 'OG001'}]}]}, {'title': 'Concentration of myoinositol in PCGM', 'categories': [{'measurements': [{'value': '3.80', 'spread': '0.80', 'groupId': 'OG000'}, {'value': '4.37', 'spread': '0.46', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.001', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori threshold is 0.05.', 'groupDescription': 'The null hypothesis predicts that the concentration of glutamine is the same for controls and OTCD patients in PCGM.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}, {'pValue': '0.011', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold is 0.05.', 'groupDescription': 'The null hypothesis predicts that the concentration of myoinositol is the same for controls and OTCD patients in PCGM.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}, {'pValue': '0.004', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori threshold was 0.05.', 'groupDescription': 'The null hypothesis predicts that the concentration of glutamine is the same for controls and OTCD patients in PWM.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}, {'pValue': '0.046', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori threshold was 0.05.', 'groupDescription': 'The null hypothesis predicts that the concentration of myoinositol is the same for controls and OTCD patients in PWM.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline', 'description': "Concentration based on area under curve on 1H Magnetic Resonance Spectroscopy(MRS) and quantitated by LCModel (a method that allows automatic quantitation of spectroscopy data). A metabolite's tissue concentration is related to the integrated amplitude, the area under the curve of the MRS signal, it produces. While MRS signals are usually acquired in the time domain as free induction decays or echoes, they are usually viewed and analyzed in the frequency domain. The frequency domain representation is derived from the acquired time domain data by the Fourier Transform. The protocol we use selects 257 averages. The machine summates the data at each time point to generate one value for the area under the curve. Therefore, we don't have the measurement at each time point.\n\nFurthermore, we measured voxels in two different brain areas containing different kinds of brain matter: one voxel was located in posterior cingulate gray matter (PCGM) and the other in parietal white matter (PWM).", 'unitOfMeasure': 'mM', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Two OTCD patients and one healthy control were excluded due to excessive head motion.'}, {'type': 'PRIMARY', 'title': 'Functional Connectivity of Assessed by Resting-state fMRI', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '22', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Subjects With OTCD', 'description': 'males and females ages 7-60 years with OTCD\n\nMRI scanning: 1H MRS, DTI, FMRI\n\nCognitive testing: Neuropsychological testing'}, {'id': 'OG001', 'title': 'Healthy Controls', 'description': 'males and females ages 7-60 years who are healthy controls\n\nMRI scanning: 1H MRS, DTI, FMRI\n\nCognitive testing: Neuropsychological testing'}], 'classes': [{'title': 'DMN: ACC/mPFC & left IPL connectivity', 'categories': [{'measurements': [{'value': '-0.86', 'spread': '0.70', 'groupId': 'OG000'}, {'value': '0.18', 'spread': '0.30', 'groupId': 'OG001'}]}]}, {'title': 'DMN: ACC/mPFC & PCC connectivity', 'categories': [{'measurements': [{'value': '-0.10', 'spread': '0.70', 'groupId': 'OG000'}, {'value': '0.12', 'spread': '0.40', 'groupId': 'OG001'}]}]}, {'title': 'DMN: ACC/mPFC & right IPL connectivity', 'categories': [{'measurements': [{'value': '-0.26', 'spread': '0.53', 'groupId': 'OG000'}, {'value': '0.07', 'spread': '0.34', 'groupId': 'OG001'}]}]}, {'title': 'DMN: PCC & left IPL connectivity', 'categories': [{'measurements': [{'value': '0.69', 'spread': '0.63', 'groupId': 'OG000'}, {'value': '0.69', 'spread': '0.31', 'groupId': 'OG001'}]}]}, {'title': 'DMN: PCC & right IPL connectivity', 'categories': [{'measurements': [{'value': '0.66', 'spread': '0.42', 'groupId': 'OG000'}, {'value': '0.64', 'spread': '0.30', 'groupId': 'OG001'}]}]}, {'title': 'DMN: left IPL & right IPL connectivity', 'categories': [{'measurements': [{'value': '0.75', 'spread': '0.69', 'groupId': 'OG000'}, {'value': '0.70', 'spread': '0.34', 'groupId': 'OG001'}]}]}, {'title': 'SMN: ACC & left aI/fO connectivity', 'categories': [{'measurements': [{'value': '0.19', 'spread': '0.39', 'groupId': 'OG000'}, {'value': '0.28', 'spread': '0.41', 'groupId': 'OG001'}]}]}, {'title': 'SMN: ACC & left SFG connectivity', 'categories': [{'measurements': [{'value': '0.28', 'spread': '0.35', 'groupId': 'OG000'}, {'value': '0.44', 'spread': '0.29', 'groupId': 'OG001'}]}]}, {'title': 'SMN: ACC & right aI/fO connectivity', 'categories': [{'measurements': [{'value': '0.21', 'spread': '0.30', 'groupId': 'OG000'}, {'value': '0.44', 'spread': '0.29', 'groupId': 'OG001'}]}]}, {'title': 'SMN: ACC & right SFG connectivity', 'categories': [{'measurements': [{'value': '0.29', 'spread': '0.37', 'groupId': 'OG000'}, {'value': '0.59', 'spread': '0.23', 'groupId': 'OG001'}]}]}, {'title': 'SMN: left aI/fO & left SFG connectivity', 'categories': [{'measurements': [{'value': '0.10', 'spread': '0.35', 'groupId': 'OG000'}, {'value': '0.22', 'spread': '0.38', 'groupId': 'OG001'}]}]}, {'title': 'SMN: left aI/fO & right aI/fO connectivity', 'categories': [{'measurements': [{'value': '0.71', 'spread': '0.43', 'groupId': 'OG000'}, {'value': '0.80', 'spread': '0.35', 'groupId': 'OG001'}]}]}, {'title': 'SMN: left aI/fO & right SFG connectivity', 'categories': [{'measurements': [{'value': '0.05', 'spread': '0.33', 'groupId': 'OG000'}, {'value': '0.11', 'spread': '0.33', 'groupId': 'OG001'}]}]}, {'title': 'SMN: left SFG & right SFG connectivity', 'categories': [{'measurements': [{'value': '0.70', 'spread': '0.43', 'groupId': 'OG000'}, {'value': '0.68', 'spread': '0.28', 'groupId': 'OG001'}]}]}, {'title': 'SMN: right aI/fO & left SFG connectivity', 'categories': [{'measurements': [{'value': '0.02', 'spread': '0.22', 'groupId': 'OG000'}, {'value': '0.25', 'spread': '0.21', 'groupId': 'OG001'}]}]}, {'title': 'SMN: right aI/fO & right SFG connectivity', 'categories': [{'measurements': [{'value': '0.04', 'spread': '0.26', 'groupId': 'OG000'}, {'value': '0.27', 'spread': '0.35', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'Our a priori threshold for statistical significance was 0.05.', 'groupDescription': 'The null hypothesis states predicts no main effects of Group, ROI pair, or Age, suggesting that the connectivity between all DMN nodes is the same across groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a 2 (Group) x 6 (ROI Pair) ANOVA to assess functional connectivity between the nodes of the DMN, using age as a covariate.'}, {'pValue': '0.024', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold was 0.05.', 'groupDescription': 'The null hypothesis predicts that functional connectivity between the ACC/mPFC node and the left IPL node does not differ between groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a series of post-hoc one-way ANOVAs to localize the main effect found. Age was used as a covariate.'}, {'pValue': '0.040', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold is 0.05.', 'groupDescription': 'The null hypothesis predicts that functional connectivity between the ACC/mPFC node and the PCC node does not differ between groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a series of post-hoc one-way ANOVAs to localize the main effect found. Age was used as a covariate.'}, {'pValue': '0.008', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold was 0.05', 'groupDescription': 'The null hypothesis predicts that functional connectivity between the ACC/mPFC node and the right IPL node does not differ between groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a series of post-hoc one-way ANOVAs to localize the main effect found. Age was used as a covariate.'}, {'pValue': '0.470', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold was 0.05', 'groupDescription': 'The null hypothesis predicts that functional connectivity between the left IPL node and the right IPL node does not differ between groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a series of post-hoc one-way ANOVAs to localize the main effect found. Age was used as a covariate.'}, {'pValue': '0.829', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold was 0.05', 'groupDescription': 'The null hypothesis predicts that functional connectivity between the PCC node and the left IPL node does not differ between groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a series of post-hoc one-way ANOVAs to localize the main effect found. Age was used as a covariate.'}, {'pValue': '0.801', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold was 0.05', 'groupDescription': 'The null hypothesis predicts that functional connectivity between the PCC node and the right IPL node does not differ between groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a series of post-hoc one-way ANOVAs to localize the main effect found. Age was used as a covariate.'}, {'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'Our a priori threshold for statistical significance was 0.05.', 'groupDescription': 'The null hypothesis states predicts no main effects of Group, ROI pair, or Age, suggesting that the connectivity between all SMN nodes is the same across groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a 2 (Group) x 6 (ROI Pair) ANOVA to assess functional connectivity between the nodes of the SMN, using age as a covariate.'}, {'pValue': '0.550', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold was 0.05.', 'groupDescription': 'The null hypothesis predicts that functional connectivity between the ACC node and the left aI/fO node does not differ between groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a series of post-hoc one-way ANOVAs to localize the main effect found. Age was used as a covariate.'}, {'pValue': '0.113', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold was 0.05.', 'groupDescription': 'The null hypothesis predicts that functional connectivity between the ACC node and the left SFG node does not differ between groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a series of post-hoc one-way ANOVAs to localize the main effect found. Age was used as a covariate.'}, {'pValue': '0.039', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold was 0.05.', 'groupDescription': 'The null hypothesis predicts that functional connectivity between the ACC node and the right aI/fO node does not differ between groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a series of post-hoc one-way ANOVAs to localize the main effect found. Age was used as a covariate.'}, {'pValue': '0.005', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold was 0.05.', 'groupDescription': 'The null hypothesis predicts that functional connectivity between the ACC node and the right SFG node does not differ between groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a series of post-hoc one-way ANOVAs to localize the main effect found. Age was used as a covariate.'}, {'pValue': '0.426', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold was 0.05.', 'groupDescription': 'The null hypothesis predicts that functional connectivity between the left aI/fO and the left SFG node does not differ between groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a series of post-hoc one-way ANOVAs to localize the main effect found. Age was used as a covariate.'}, {'pValue': '0.256', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold was 0.05.', 'groupDescription': 'The null hypothesis predicts that functional connectivity between the left aI/fO node and the right aI/fO node does not differ between groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a series of post-hoc one-way ANOVAs to localize the main effect found. Age was used as a covariate.'}, {'pValue': '0.853', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold was 0.05.', 'groupDescription': 'The null hypothesis predicts that functional connectivity between the left aI/fO and the right SFG node does not differ between groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a series of post-hoc one-way ANOVAs to localize the main effect found. Age was used as a covariate.'}, {'pValue': '0.003', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold was 0.05.', 'groupDescription': 'The null hypothesis predicts that functional connectivity between the right aI/fO node and the left SFG node does not differ between groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a series of post-hoc one-way ANOVAs to localize the main effect found. Age was used as a covariate.'}, {'pValue': '0.023', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'This is an uncorrected p-value. A priori significance threshold was 0.05.', 'groupDescription': 'The null hypothesis predicts that functional connectivity between the right aI/fO node and the right SFG node does not differ between groups.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'We ran a series of post-hoc one-way ANOVAs to localize the main effect found. Age was used as a covariate.'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline', 'description': "Investigation of differences in functional connectivity of OTCD patients compared to healthy controls, particularly in the default-mode network (DMN) and the set-maintenance network (SMN). Participants underwent a resting-state scan using 3T fMRI. Combining independent component analysis (ICA) and region-of-interest (ROI) analyses, identified the nodes that comprised each network in each group, and assessed internodal connectivity. For each subject, this analysis generated a correlation value, which reflected the strength of functional connectivity between each ROI pair.The correlation r-values were normalized using Fisher's r-to-Z-transform, generating z-scores. The DMN was composed of 1) anterior cingulate/medial prefrontal cortex (ACC/mPFC), 2) posterior cingulate cortex (PCC), and 3) bilateral inferior parietal lobule (IPL). The SMN was composed of 1)ACC, 2) bilateral superior frontal gyrus (SFG), and 3) bilateral anterior insula/frontal operculum (aI/fO).", 'unitOfMeasure': 'z-scores', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Resting state data was not acquired for several of our participants (7 controls and 4 patients). Furthermore, 3 OTCD patients were excluded from the analyses due to excessive head motion.'}, {'type': 'PRIMARY', 'title': 'Fractional Anisotropy Assessed Using DTI', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Subjects With OTCD', 'description': 'males and females ages 7-60 years with OTCD\n\nMRI scanning: 1H MRS, DTI, FMRI\n\nCognitive testing: Neuropsychological testing'}, {'id': 'OG001', 'title': 'Healthy Controls', 'description': 'males and females ages 7-60 years who are healthy controls\n\nMRI scanning: 1H MRS, DTI, FMRI\n\nCognitive testing: Neuropsychological testing'}], 'classes': [{'categories': [{'measurements': [{'value': '0.25', 'spread': '0.003', 'groupId': 'OG000'}, {'value': '0.3', 'spread': '0.008', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline', 'description': 'Fractional Anisotropy (FA) is a measure of the diffusion asymmetry within a voxel as defined by its eigenvalues. In our study, FA is being used as a measure of white matter integrity, because FA is very sensitive to small microstructural changes.Fractional anisotropy (FA) is a scalar value between zero and one (0-1) that describe anisotropy of a diffusion process. A value of zero means that diffusion is isotropic, i.e. it is unrestricted (or equally restricted) in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Neuropsychological Assessment', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '29', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Subjects With OTCD', 'description': 'males and females ages 7-60 years with OTCD\n\nMRI scanning: 1H MRS, DTI, FMRI\n\nCognitive testing: Neuropsychological testing'}, {'id': 'OG001', 'title': 'Healthy Controls', 'description': 'males and females ages 7-60 years who are healthy controls\n\nMRI scanning: 1H MRS, DTI, FMRI\n\nCognitive testing: Neuropsychological testing'}], 'classes': [{'title': 'WASI - Verbal IQ', 'categories': [{'measurements': [{'value': '107.33', 'spread': '14.52', 'groupId': 'OG000'}, {'value': '107.77', 'spread': '18.59', 'groupId': 'OG001'}]}]}, {'title': 'WASI - Performance IQ', 'categories': [{'measurements': [{'value': '98.5', 'spread': '13.14', 'groupId': 'OG000'}, {'value': '112.59', 'spread': '14.54', 'groupId': 'OG001'}]}]}, {'title': 'WASI - Full IQ', 'categories': [{'measurements': [{'value': '103.28', 'spread': '14.02', 'groupId': 'OG000'}, {'value': '111.22', 'spread': '16.89', 'groupId': 'OG001'}]}]}, {'title': 'Trails - Composite', 'categories': [{'measurements': [{'value': '48', 'spread': '15', 'groupId': 'OG000'}, {'value': '47', 'spread': '12', 'groupId': 'OG001'}]}]}, {'title': 'Brief - Behavioral Regulation Index (BRI)', 'categories': [{'measurements': [{'value': '55.59', 'spread': '9.49', 'groupId': 'OG000'}, {'value': '46.73', 'spread': '8.90', 'groupId': 'OG001'}]}]}, {'title': 'Brief - Metacognition Index (MI)', 'categories': [{'measurements': [{'value': '60.45', 'spread': '11.75', 'groupId': 'OG000'}, {'value': '47.38', 'spread': '8.22', 'groupId': 'OG001'}]}]}, {'title': 'Brief - Global Executive Composite Score (GEC)', 'categories': [{'measurements': [{'value': '59.05', 'spread': '10.37', 'groupId': 'OG000'}, {'value': '46.88', 'spread': '7.67', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.929', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'Equal variance is not assumed. Two tailed t-test WASI verbal IQ between cases and controls', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}, {'pValue': '.002', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'Equal variance not assumed. Comparison WASI performance IQ cases and controls', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}, {'pValue': '.094', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'Equal variance not assumed. Comparison of WASI full IQ cases and controls', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}, {'pValue': '.853', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'Equal variance not assumed. Comparison of CTMT global composite score between cases and controls', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}, {'pValue': '.001', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'Equal variance not assumed. Comparison of BRIEF BRI cases and controls', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}, {'pValue': '<.001', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'Equal variances not assumed. Comparison of BRIEF MI cases and controls', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}, {'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'Equal variances not assumed. Comparison of BRIEF GEC between cases and controls.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline', 'description': 'Testing consisted of the Wechsler Abbreviated Scale of Intelligence (WASI), Comprehensive Trail Making Test (CTMT) (range 17-87), and the Behavioral Rating Inventory of Executive Function (BRIEF) (range GEC: 70-210; BRI:39-82 ; MI:41-92). The WASI includes three measures of intelligence; including, performance IQ (sum of block design and matrices sub scales; range: 40-160), verbal IQ (sum of vocabulary and similarities sub scales; range 40-160), and total IQ (sum of all four subscales; range: 80-320). The CTMT measures simple attention and executive function, it consists of five dot to dots that increase with complexity and difficulty. Higher values indicate better outcomes for all scales.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Subjects With OTCD', 'description': 'males and females ages 7-60 years with OTCD\n\nMRI scanning: 1H Magnetic Resonance Spectroscopy (MRS), Diffusion Tensor Imaging (DTI), functional magnetic resonance imaging (fMRI)\n\nCognitive testing: Neuropsychological testing'}, {'id': 'FG001', 'title': 'Healthy Controls', 'description': 'males and females ages 7-60 years who are healthy controls\n\nMRI scanning: 1H MRS, DTI, FMRI\n\nCognitive testing: Neuropsychological testing'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '20'}, {'groupId': 'FG001', 'numSubjects': '29'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '20'}, {'groupId': 'FG001', 'numSubjects': '27'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '2'}]}], 'dropWithdraws': [{'type': 'Physician Decision', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '2'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'BG000'}, {'value': '27', 'groupId': 'BG001'}, {'value': '47', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Subjects With OTCD', 'description': 'males and females ages 7-60 years with OTCD\n\nMRI scanning: 1H MRS, DTI, FMRI\n\nCognitive testing: Neuropsychological testing'}, {'id': 'BG001', 'title': 'Healthy Controls', 'description': 'males and females ages 7-60 years who are healthy controls\n\nMRI scanning: 1H MRS, DTI, FMRI\n\nCognitive testing: Neuropsychological testing'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '30.3', 'spread': '19.4', 'groupId': 'BG000'}, {'value': '25.8', 'spread': '14.6', 'groupId': 'BG001'}, {'value': '28.05', 'spread': '17.02', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '17', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '36', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '11', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 49}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-09'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-02', 'completionDateStruct': {'date': '2014-08', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-02-10', 'studyFirstSubmitDate': '2012-03-30', 'resultsFirstSubmitDate': '2015-06-30', 'studyFirstSubmitQcDate': '2012-04-02', 'lastUpdatePostDateStruct': {'date': '2024-03-08', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2017-04-12', 'studyFirstPostDateStruct': {'date': '2012-04-03', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2017-04-14', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2014-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Concentration of Glutamine and Myoinositol', 'timeFrame': 'Baseline', 'description': "Concentration based on area under curve on 1H Magnetic Resonance Spectroscopy(MRS) and quantitated by LCModel (a method that allows automatic quantitation of spectroscopy data). A metabolite's tissue concentration is related to the integrated amplitude, the area under the curve of the MRS signal, it produces. While MRS signals are usually acquired in the time domain as free induction decays or echoes, they are usually viewed and analyzed in the frequency domain. The frequency domain representation is derived from the acquired time domain data by the Fourier Transform. The protocol we use selects 257 averages. The machine summates the data at each time point to generate one value for the area under the curve. Therefore, we don't have the measurement at each time point.\n\nFurthermore, we measured voxels in two different brain areas containing different kinds of brain matter: one voxel was located in posterior cingulate gray matter (PCGM) and the other in parietal white matter (PWM)."}, {'measure': 'Functional Connectivity of Assessed by Resting-state fMRI', 'timeFrame': 'Baseline', 'description': "Investigation of differences in functional connectivity of OTCD patients compared to healthy controls, particularly in the default-mode network (DMN) and the set-maintenance network (SMN). Participants underwent a resting-state scan using 3T fMRI. Combining independent component analysis (ICA) and region-of-interest (ROI) analyses, identified the nodes that comprised each network in each group, and assessed internodal connectivity. For each subject, this analysis generated a correlation value, which reflected the strength of functional connectivity between each ROI pair.The correlation r-values were normalized using Fisher's r-to-Z-transform, generating z-scores. The DMN was composed of 1) anterior cingulate/medial prefrontal cortex (ACC/mPFC), 2) posterior cingulate cortex (PCC), and 3) bilateral inferior parietal lobule (IPL). The SMN was composed of 1)ACC, 2) bilateral superior frontal gyrus (SFG), and 3) bilateral anterior insula/frontal operculum (aI/fO)."}, {'measure': 'Fractional Anisotropy Assessed Using DTI', 'timeFrame': 'Baseline', 'description': 'Fractional Anisotropy (FA) is a measure of the diffusion asymmetry within a voxel as defined by its eigenvalues. In our study, FA is being used as a measure of white matter integrity, because FA is very sensitive to small microstructural changes.Fractional anisotropy (FA) is a scalar value between zero and one (0-1) that describe anisotropy of a diffusion process. A value of zero means that diffusion is isotropic, i.e. it is unrestricted (or equally restricted) in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions.'}], 'secondaryOutcomes': [{'measure': 'Neuropsychological Assessment', 'timeFrame': 'Baseline', 'description': 'Testing consisted of the Wechsler Abbreviated Scale of Intelligence (WASI), Comprehensive Trail Making Test (CTMT) (range 17-87), and the Behavioral Rating Inventory of Executive Function (BRIEF) (range GEC: 70-210; BRI:39-82 ; MI:41-92). The WASI includes three measures of intelligence; including, performance IQ (sum of block design and matrices sub scales; range: 40-160), verbal IQ (sum of vocabulary and similarities sub scales; range 40-160), and total IQ (sum of all four subscales; range: 80-320). The CTMT measures simple attention and executive function, it consists of five dot to dots that increase with complexity and difficulty. Higher values indicate better outcomes for all scales.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Neuroimaging', 'MRI', 'Urea cycle', 'hyperammonemia', 'cognitive function', 'ornithine transcarbamylase deficiency'], 'conditions': ['Ornithine Transcarbamylase Deficiency']}, 'referencesModule': {'references': [{'pmid': '22110002', 'type': 'BACKGROUND', 'citation': 'Gropman AL, Shattuck K, Prust MJ, Seltzer RR, Breeden AL, Hailu A, Rigas A, Hussain R, VanMeter J. Altered neural activation in ornithine transcarbamylase deficiency during executive cognition: an fMRI study. Hum Brain Mapp. 2013 Apr;34(4):753-61. doi: 10.1002/hbm.21470. Epub 2011 Nov 23.'}, {'pmid': '21778100', 'type': 'BACKGROUND', 'citation': 'Prust MJ, Gropman AL, Hauser N. New frontiers in neuroimaging applications to inborn errors of metabolism. Mol Genet Metab. 2011 Nov;104(3):195-205. doi: 10.1016/j.ymgme.2011.06.020. Epub 2011 Jun 30.'}, {'pmid': '20488904', 'type': 'BACKGROUND', 'citation': 'Gropman AL, Gertz B, Shattuck K, Kahn IL, Seltzer R, Krivitsky L, Van Meter J. Diffusion tensor imaging detects areas of abnormal white matter microstructure in patients with partial ornithine transcarbamylase deficiency. AJNR Am J Neuroradiol. 2010 Oct;31(9):1719-23. doi: 10.3174/ajnr.A2122. Epub 2010 May 20.'}, {'pmid': '20207564', 'type': 'BACKGROUND', 'citation': 'Gropman A. Brain imaging in urea cycle disorders. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S20-30. doi: 10.1016/j.ymgme.2010.01.017. Epub 2010 Feb 13.'}, {'pmid': '20004862', 'type': 'BACKGROUND', 'citation': 'Oldham MS, VanMeter JW, Shattuck KF, Cederbaum SD, Gropman AL. Diffusion tensor imaging in arginase deficiency reveals damage to corticospinal tracts. Pediatr Neurol. 2010 Jan;42(1):49-52. doi: 10.1016/j.pediatrneurol.2009.07.017.'}, {'pmid': '19567648', 'type': 'BACKGROUND', 'citation': 'Gropman AL, Sailasuta N, Harris KC, Abulseoud O, Ross BD. Ornithine transcarbamylase deficiency with persistent abnormality in cerebral glutamate metabolism in adults. Radiology. 2009 Sep;252(3):833-41. doi: 10.1148/radiol.2523081878. Epub 2009 Jun 30.'}, {'pmid': '18662894', 'type': 'BACKGROUND', 'citation': 'Gropman AL, Fricke ST, Seltzer RR, Hailu A, Adeyemo A, Sawyer A, van Meter J, Gaillard WD, McCarter R, Tuchman M, Batshaw M; Urea Cycle Disorders Consortium. 1H MRS identifies symptomatic and asymptomatic subjects with partial ornithine transcarbamylase deficiency. Mol Genet Metab. 2008 Sep-Oct;95(1-2):21-30. doi: 10.1016/j.ymgme.2008.06.003. Epub 2008 Jul 26.'}], 'seeAlsoLinks': [{'url': 'http://NUCDF.org', 'label': 'Family support group'}, {'url': 'https://ucdc.rarediseasesnetwork.org/', 'label': 'Urea Cycle rare disease consortium'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to use various types of MRI and cognitive testing to evaluate changes in the brain and cognitive function that occur in subjects with ornithine transcarbamylase deficiency (OTCD) relative to healthy individuals', 'detailedDescription': 'The overall goal of this project is to characterize metabolic, structural and cognitive changes in OTCD using 1H MRS, DTI, volumetric averaging and fMRI with cognitive testing of executive function measures to validate biomarkers for the effect of HA and its treatment on the brain.\n\nThe investigators will measure gln and mI in blood and brain (using 1H MRS) in affected participants, and mI in brain in controls, fractional anisotropy as a measure of white matter microstructural damage (by DTI) and brain activation pathways alterations with tasks probing working memory (fMRI). As a secondary outcome measure, the investigators will correlate the findings from neuroimaging with cognitive functioning. This protocol is based on the previous 5104 protocol, now includes children to evaluate the age and stage of disease on these indices in a cohort that is undergoing important developmental events against an age matched typically developing cohort.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '60 Years', 'minimumAge': '7 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': 'Males and females, ages 7-60 years with ornithine transcarbamylase deficiency Males and females, ages 7-60 years who are healthy controls without ornithine transcarbamylase deficiency', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\nSubject inclusion criteria:\n\n1. Patients with OTCD;\n2. Age range: 7-60 years\n3. Able to undergo neuroimaging safely (i.e. without presence of ferromagnetic devices)\n4. Subject has a documented full scale IQ \\> 70\n\nControl participant inclusion criteria:\n\n1. Healthy males and females without metabolic disease aged 7-60 years\n2. Subject has a documented full scale IQ \\> 70\n\nExclusion Criteria:\n\nSubject exclusion criteria:\n\n1. Mental retardation (i.e., Full Scale IQ\\< 70)\n2. Age range \\<7 or \\>60 years\n3. Presence of ferromagnetic device(s) that preclude safe imaging\n4. Pregnant female\n\nControl exclusion criteria:\n\n1. Subjects with a documented history of an intellectual deficit (i.e., Full Scale IQ\\< 70)\n2. Age range \\<7 or \\>60 years\n3. Presence of ferromagnetic device(s) that preclude safe imaging\n4. Pregnant female'}, 'identificationModule': {'nctId': 'NCT01569568', 'briefTitle': 'Investigation of Brain Nitrogen in Partial Ornithine Transcarbamylase Deficiency (OTCD) Using 1 H MRS, DTI, and fMRI', 'organization': {'class': 'OTHER', 'fullName': "Children's National Research Institute"}, 'officialTitle': 'Investigation of Brain Nitrogen in Partial Ornithine Transcarbamylase Deficiency (OTCD) Using 1 H MRS, DTI, and fMRI', 'orgStudyIdInfo': {'id': 'UCRDC 5107'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Subjects with OTCD', 'description': 'males and females ages 7-60 years with OTCD who are able to undergo MRI and cognitive testing MRI scanning\n\n1H MRS, DTI, FMRI Cognitive testing Neuropsychological testing', 'interventionNames': ['Other: MRI scanning', 'Behavioral: Cognitive testing']}, {'label': 'Healthy controls', 'description': 'males and females ages 7-60 years who are healthy controls who are able to undergo MRI and cognitive testing MRI scanning\n\n1H MRS, DTI, FMRI Cognitive testing Neuropsychological testing', 'interventionNames': ['Other: MRI scanning', 'Behavioral: Cognitive testing']}], 'interventions': [{'name': 'MRI scanning', 'type': 'OTHER', 'otherNames': ['MRI'], 'description': '1H MRS, DTI, FMRI', 'armGroupLabels': ['Healthy controls', 'Subjects with OTCD']}, {'name': 'Cognitive testing', 'type': 'BEHAVIORAL', 'description': 'Behavioral testing', 'armGroupLabels': ['Healthy controls', 'Subjects with OTCD']}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'Andrea L Gropman, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Children's National Research Institute"}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES', 'description': 'Final data is on the UCDC website'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Andrea Gropman', 'class': 'OTHER'}, 'collaborators': [{'name': "Children's National Research Institute", 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'MD', 'investigatorFullName': 'Andrea Gropman', 'investigatorAffiliation': "Children's National Research Institute"}}}}