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| ID | Type | Description | Link |
|---|---|---|---|
| U54RR019453 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Office of Rare Diseases (ORD) | NIH |
| Rare Diseases Clinical Research Network | NETWORK |
| National Center for Research Resources (NCRR) | NIH |
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Urea cycle disorders (UCDs) are a group of rare inherited metabolism disorders. The purpose of this study is to evaluate how UCD-related neurologic injuries affect adults with one of the most common types of UCD.
UCDs are a group of rare genetic diseases that affect how protein is broken down in the body. The cause of UCDs is a deficiency in one of eight enzymes responsible for removing ammonia, a waste product of protein metabolism, from the bloodstream. Normally, ammonia is converted into urea and then removed from the body in the form of urine. However, in people with UCDs, ammonia accumulates unchecked and is not removed from the body. Toxic levels of ammonia can build up and cause irreversible neurologic damage that can affect metabolism, cognition, sensation, and movement. This study will focus on the most common enzyme disorder among UCDs, ornithine transcarbamylase deficiency (OTCD), a disorder inherited from mothers. Using different types of magnetic resonance imaging (MRI), this study will evaluate how UCD-related neurologic injuries affect metabolism, cognition, sensation, and movement in adults with OTCD.
Participants in this study will attend an initial study visit that will include a review of medical history, current symptoms, impairments, and diet history; urine and blood collection; a physical exam; a full neurological exam; and cognitive and motor testing. During this visit, participants will undergo imaging studies and additional cognitive and motor testing over a 2- to 3-day period. This will include standard MRI studies and four sessions consisting of functional MRI (fMRI), diffusion tensor imaging, and 1H magnetic resonance spectroscopy. For the fMRI study, participants perform various motor and behavioral tasks while in the imaging scanner. Magnetic resonance spectroscopy (MRS) is used to study and evaluate the chemical makeup of specific brain areas. Diffusion tensor imaging is used to assess myelination of major brain pathways and their alteration in disease states. This study will involve one-time participation. There will be no follow-up visits for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD | ||
| 2 | Healthy males or females without known medical or metabolic disorder (control group) |
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| Measure | Description | Time Frame |
|---|---|---|
| Concentration of Glutamine and Myoinositol by MRS | Concentration based on area under curve on 1H MRS and quantitated by LCModel. A metabolite's tissue concentration is related to the integrated amplitude of the MRS signal it produces. Integrated amplitude is the area under the MRS signal curve. 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. This means, 257 free induction decays. 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. Furthermore, 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). | one time measurement at study baseline |
| Functional MRI Activation in N-Back Tast | Measure of blood oxygen level dependent (BOLD) signal of OTCD patients and healthy controls during an N-Back task comparing 2-back and 1-back conditions. This contrast was created for each participant using SPM and then entered into a group analysis in which we compare percent signal change between groups. Therefore, we never see BOLD signal change at the individual level, which is why we never see "scores" or numbers at the individual level and we cannot calculate a measure of dispersion for this data. | one time measurement at study baseline |
| Fractional Anisotropy | Measure of white matter integrity in OTCD Patients and Controls in frontal white matter. Fractional anisotropy values fall on a scale of 0 to 1, with 0 meaning that the diffusion of water is isotropic and unrestricted, or equally restricted, in all directions and with 1 meaning that diffusion occurs along only one axis and is fully restricted along all other directions. Scores closer to 1 are associated with intact white matter while scores closer to 0 are associated with white matter damage. | one time measurement at study baseline |
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Inclusion Criteria for Participants with OTCD:
Inclusion Criteria for Healthy Controls:
Inclusion Criteria for All Participants:
Exclusion Criteria for All Participants:
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Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD
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| Name | Affiliation | Role |
|---|---|---|
| Andrea Gropman, MD | Children's National Research Institute | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| George Washington University School of Medicine | Washington D.C. | District of Columbia | 20037 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 14705115 | Background | Gyato K, Wray J, Huang ZJ, Yudkoff M, Batshaw ML. Metabolic and neuropsychological phenotype in women heterozygous for ornithine transcarbamylase deficiency. Ann Neurol. 2004 Jan;55(1):80-6. doi: 10.1002/ana.10794. | |
| 12536032 | Background | Kurihara A, Takanashi Ji, Tomita M, Kobayashi K, Ogawa A, Kanazawa M, Yamamoto S, Kohno Y. Magnetic resonance imaging in late-onset ornithine transcarbamylase deficiency. Brain Dev. 2003 Jan;25(1):40-4. doi: 10.1016/s0387-7604(02)00153-5. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Female Carriers of Ornithine Transcarbamylase Deficiency (OTCD | Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD |
| FG001 | Healthy Males or Females Without Known Medical or Metabolic di | Healthy males or females without known medical or metabolic disorder (control group) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Half of the subjects were affected and half were normal controls age 18-60
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| ID | Title | Description |
|---|---|---|
| BG000 | Female Carriers of Ornithine Transcarbamylase Deficiency (OTCD | Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD |
| BG001 | Healthy Males or Females Without Known Medical or Metabolic di |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Concentration of Glutamine and Myoinositol by MRS | Concentration based on area under curve on 1H MRS and quantitated by LCModel. A metabolite's tissue concentration is related to the integrated amplitude of the MRS signal it produces. Integrated amplitude is the area under the MRS signal curve. 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. This means, 257 free induction decays. 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. Furthermore, 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). | Posted | Mean | Standard Deviation | mM | one time measurement at study baseline |
|
Entire study
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | OTCD Patients | Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD |
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This study examined the neurobiological differences between OTCD patients and controls. This was, however, not a clinical trial, since participants received no form of drug therapy or treatment as part of this study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Andrea Gropman, M.D. | Children's Research Institute | 202-476-2120 | agropman@childrensnational.org |
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| ID | Term |
|---|---|
| D020739 | Brain Diseases, Metabolic, Inborn |
| D056806 | Urea Cycle Disorders, Inborn |
| D020163 | Ornithine Carbamoyltransferase Deficiency Disease |
| ID | Term |
|---|---|
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| Georgetown University |
| Washington D.C. |
| District of Columbia |
| 20057 |
| United States |
| 10946359 | Background | McCullough BA, Yudkoff M, Batshaw ML, Wilson JM, Raper SE, Tuchman M. Genotype spectrum of ornithine transcarbamylase deficiency: correlation with the clinical and biochemical phenotype. Am J Med Genet. 2000 Aug 14;93(4):313-9. doi: 10.1002/1096-8628(20000814)93:43.0.co;2-m. |
Healthy males or females without known medical or metabolic disorder (control group) |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OTCD Patients |
Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD |
| OG001 | Healthy Controls | Healthy males or females without known medical or metabolic disorder (control group) |
|
|
|
| Primary | Functional MRI Activation in N-Back Tast | Measure of blood oxygen level dependent (BOLD) signal of OTCD patients and healthy controls during an N-Back task comparing 2-back and 1-back conditions. This contrast was created for each participant using SPM and then entered into a group analysis in which we compare percent signal change between groups. Therefore, we never see BOLD signal change at the individual level, which is why we never see "scores" or numbers at the individual level and we cannot calculate a measure of dispersion for this data. | Five OTCD patients and one healthy control were excluded due to excessive head motion. | Posted | Number | percent signal change | one time measurement at study baseline |
|
|
|
|
| Primary | Fractional Anisotropy | Measure of white matter integrity in OTCD Patients and Controls in frontal white matter. Fractional anisotropy values fall on a scale of 0 to 1, with 0 meaning that the diffusion of water is isotropic and unrestricted, or equally restricted, in all directions and with 1 meaning that diffusion occurs along only one axis and is fully restricted along all other directions. Scores closer to 1 are associated with intact white matter while scores closer to 0 are associated with white matter damage. | Five OTCD Patients and four healthy controls were excluded due to excessive head motion. | Posted | Mean | Standard Deviation | units on a scale | one time measurement at study baseline |
|
|
|
|
| 0 |
| 24 |
| 0 |
| 24 |
| EG001 | Healthy Controls | Healthy males or females without known medical or metabolic disorder (control group) | 0 | 22 | 0 | 22 |
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| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D000592 | Amino Acid Metabolism, Inborn Errors |
| D040181 | Genetic Diseases, X-Linked |
| Anterior cingulate cortex (BA 32) |
|