Urea Cycle DisordersUCDNCT02935283
Neuroimaging and Neuropsychological Outcomes in Urea Cycle Disorders
An observational study of Urea Cycle Disorders, run by Children's National Research Institute at 1 site in United States.
Trial summary
In proximal urea cycle disorders (UCD), particularly ornithine transcarbamylase deficiency (OTCD), hyperammonemia (HA) causes increased brain glutamine (Gln) which perturbation is thought to be at the core of the neurological injury. Read more about this study
- Who is it for?
- Ages 7 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Urea Cycle Disorders
- What is being tested?
- MRI and Behavioral
- Type of treatment
- Surgery or procedure, Lifestyle or therapy programme
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2016to Dec 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 50 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: Participants have a urea cycle disorder or are healthy controls ages 7-30 years, male and female. Participants who have had a recent hyperammonemic episode are eligible for a more detailed analysis.
Who may be able to join
- Confirmed diagnosis of ornithine transcarbamylase deficiency (OTCD) by genetic analysis (genotype) and/or enzyme analysis with at least a single episode of HA hyperammonemic (HA) encephalopathy
- Ability to undergo MRI without sedation
- Ages 7 - 50 years
- Ability to provide informed consent or assent to the procedures
- Healthy controls (age and gender matched)
- Males and females with a UCD who are having an acute metabolic crisis, with ammonia levels between 100-300 µM
Show all 16Show fewer
- Subjects must be awake, and not comatose and able to maintain patent airway on their own and in the opinion of the examining physician, medically stable without risk for acute decompensation and must continue to be stable based on visual contact, vital sign measurement and voice contact with subjects while in the scanner
- Age range 7-30 years
- Able to undergo neuroimaging safely (i.e. without ferromagnetic devices)
- Sexually active female of childbearing potential must agree to urine pregnancy test
- Admitted to the hospital for treatment of HA at one of the 4 sites for this study
- Can be subjects who were originally enrolled in aim 1 who then have HA (they will cross over to aim 2)
- Confirmed diagnosis of arginosuccinate ASSD, and ASLD by genotype and/or enzyme analysis or healthy age and gender matched control
- Ability to undergo MRI without sedation
- Age 7 - 30 years
- Able to provide informed consent or assent to the procedures
Who cannot join
- Inability to undergo MRI without sedation
- Metal implants, including orthodontic braces
- Other health conditions contra-indicated in MRI
- Medically unstable at time of scheduled research visit
- Unable to provide informed consent or assent to the procedures
- Ammonia level > 300 µM, or <100 µM
Show all 18Show fewer
- Presence of coma and/or inability to maintain a patent airway
- Age <7 or >30 years
- Subject with ferromagnetic device that precludes safe MRI imaging
- Pregnant female
- Unstable medically, at risk for decompensations
- Combative, or severely neurologically compromised irrespective of ammonia level and showing declining medical status in the scanner based on visual, voice contact and electronic HR monitoring.
- Subjects must be awake, and not comatose and able to maintain patent airway on their own
- Inability to undergo MRI without sedation
- Metal implants, including orthodontic braces
- Other health conditions contra-indicated for MRI
- Medically unstable at time of scheduled research visit
- Unable to provide informed consent or assent
Trial locations and contacts
1 site in 1 country.
Andrea L. Gropman, M.D. contact
United States1 site, 1 recruiting
- Recruiting
Children's Research Institute
Washington D.C., District of Columbia, 20010
Andrea L. Gropman, M.D., 202-476-3511, agropman@childrensnational.org
Andrea L Gropman, M.D.
About this study
In proximal urea cycle disorders (UCD), particularly ornithine transcarbamylase deficiency (OTCD), hyperammonemia (HA) causes increased brain glutamine (Gln) which perturbation is thought to be at the core of the neurological injury. In contrast, in distal UCD such as citrullinemia (argininosuccinate synthetase deficiency; (ASSD) and argininosuccinic aciduria (argininosuccinate lyase deficiency); (ASLD) cognitive impairment and neuropsychiatric disease are common even in the absence of acute HA. As a consequence, both citrulline and argininosuccinate (ASA) or their metabolic products have been implicated as neurotoxic. In this project the investigators will use state-of- the-art neuroimaging and neuropsychological methods to investigate whether patients with OTCD have chronically elevated brain Gln and reduced myo-inositol (mI) levels that correlate with regional brain structural abnormalities and neurocognitive dysfunction. The researchers will further investigate whether during an acute episode of HA elevated brain Gln and decreased mI levels correlate with the magnitude of cytotoxic edema and whether a Gln/mI ratio threshold can be identified at which the cytotoxic edema is followed by cell loss. Finally, the researchers will investigate whether regions of brain damage in ASSD and/or ASLD are distinct from those in OTCD and compare brain Gln levels in ASSD and ASLD in the absence of HA to those in OTCD. The investigators will also seek to determine if brain citrulline and ASA can be identified in the brains of patients with distal UCD and whether they correlate with brain abnormalities seen in MRI and neuropsychological testing. This project will elucidate the chronology of brain pathology both in acute hyperammonemia and chronic UCD and whether, proximal and distal UCD differ in their pathophysiology of brain damage.
Read the detailed description
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.
This study will be separated into three sections. The first study will study longitudinal changes in OTCD. The second section will study the recovery of OTCD participants from a hyperammonemic episode over time. The third section will be a longitudinal study of the distal urea cycle disorders. In all cases, participants in this study will attend an initial study visit that will include a review of medical history, current symptoms, impairments, and diet history; 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 1-2-day period. This will include standard MRI studies and four sessions consisting of functional MRI (fMRI) (CNMC only), 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 multiple time point participation. The study will be conducted at Children's National Medical Center and Boston Children's Hospital.
- Conditions
- Urea Cycle Disorders
- Being tested
- MRI, Behavioral
- Medical subject headings
- Urea Cycle Disorders, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRIProcedure or surgery
MRI, fMRI, 1H MRS, DTI
BehavioralBehavioural
Also called cognitive testing, Neuropsychological testing
Battery of executive function tasks
| Study group | Role | What they receive |
|---|---|---|
| OTCD participants | Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD who can undergo MRI and behavioral testing Receives: Procedure: MRI; Behavioral: Behavioral | |
| Normal controls | Healthy males or females without known medical or metabolic disorder (control group) who can undergo MRI and behavioral testing Receives: Procedure: MRI; Behavioral: Behavioral | |
| HA recovery group | Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD or participants with CPS-1 who have had a recent hyperammonemic episode who can undergo MRI and behavioral testing Receives: Procedure: MRI; Behavioral: Behavioral | |
| Distal UCD | Males and females with ASSD and ASLD who can undergo MRI and behavioral testing Receives: Procedure: MRI; Behavioral: Behavioral |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in 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 protocols used 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).
Measured: baseline and 2year follow up
Change in 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.
Measured: baseline and 2 year follow up
Secondary outcomes (1)
Change in behavioral testing results
correlation of the findings from neuroimaging with cognitive functioning that assesses executive function
Measured: baseline and 2 year follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2016 (estimated)
- Study startAug 2016
- Primary completionJul 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Urea Cycle DisordersStudies of the same condition, open and under way.
- More trials run by Children's National Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's National Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Boston Children's Hospital
- Responsible party
- Principal investigator, Andrea Gropman, Children's National Research Institute
- Investigators
- Andrea L. Gropman, M.D., Principal investigator, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02935283
- Sponsor's protocol ID
- UCD 5113
- Acronym
- UCD
- Status last verified
- Jun 2024
- First submitted
- 12 May 2016
- Last updated
- 25 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Data will be kept on UCD website and released after study completion
Publications
Pacheco-Colon I, Washington SD, Sprouse C, Helman G, Gropman AL, VanMeter JW. Reduced Functional Connectivity of Default Mode and Set-Maintenance Networks in Ornithine Transcarbamylase Deficiency. PLoS One. 2015 Jun 11;10(6):e0129595. doi: 10.1371/journal.pone.0129595. eCollection 2015.
PubMed 26067829Sprouse C, King J, Helman G, Pacheco-Colon I, Shattuck K, Breeden A, Seltzer R, VanMeter JW, Gropman AL. Investigating neurological deficits in carriers and affected patients with ornithine transcarbamylase deficiency. Mol Genet Metab. 2014 Sep-Oct;113(1-2):136-41. doi: 10.1016/j.ymgme.2014.05.007. Epub 2014 May 20.
PubMed 24881970Gropman 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.
PubMed 22110002Gropman 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.
PubMed 20488904Oldham 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.
PubMed 20004862Gropman 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.
PubMed 18662894Shapiro E, Bernstein J, Adams HR, Barbier AJ, Buracchio T, Como P, Delaney KA, Eichler F, Goldsmith JC, Hogan M, Kovacs S, Mink JW, Odenkirchen J, Parisi MA, Skrinar A, Waisbren SE, Mulberg AE. Neurocognitive clinical outcome assessments for inborn errors of metabolism and other rare conditions. Mol Genet Metab. 2016 Jun;118(2):65-9. doi: 10.1016/j.ymgme.2016.04.006. Epub 2016 Apr 14.
PubMed 27132782Waisbren SE, He J, McCarter R. Assessing Psychological Functioning in Metabolic Disorders: Validation of the Adaptive Behavior Assessment System, Second Edition (ABAS-II), and the Behavior Rating Inventory of Executive Function (BRIEF) for Identification of Individuals at Risk. JIMD Rep. 2015;21:35-43. doi: 10.1007/8904_2014_373. Epub 2015 Feb 25.
PubMed 25712381Seminara J, Tuchman M, Krivitzky L, Krischer J, Lee HS, Lemons C, Baumgartner M, Cederbaum S, Diaz GA, Feigenbaum A, Gallagher RC, Harding CO, Kerr DS, Lanpher B, Lee B, Lichter-Konecki U, McCandless SE, Merritt JL, Oster-Granite ML, Seashore MR, Stricker T, Summar M, Waisbren S, Yudkoff M, Batshaw ML. Establishing a consortium for the study of rare diseases: The Urea Cycle Disorders Consortium. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S97-105. doi: 10.1016/j.ymgme.2010.01.014. Epub 2010 Feb 10.
PubMed 20188616Jan W, Zimmerman RA, Wang ZJ, Berry GT, Kaplan PB, Kaye EM. MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation. Neuroradiology. 2003 Jun;45(6):393-9. doi: 10.1007/s00234-003-0955-7. Epub 2003 May 8.
PubMed 12736767
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroimaging and Neuropsychological Outcomes in Urea Cycle Disorders
- ClinicalTrials.gov ID
- NCT02935283
- Acronym / sponsor ID
- UCD / UCD 5113
- Conditions
- Urea Cycle Disorders
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Children's National Research InstituteUniversity, hospital or other
- Collaborators
- Boston Children's Hospital
- Study start
- Aug 2016
- Primary completion
- Jul 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 17 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In proximal urea cycle disorders (UCD), particularly ornithine transcarbamylase deficiency (OTCD), hyperammonemia (HA) causes increased brain glutamine (Gln) which perturbation is thought to be at the core of the neurological injury. In contrast, in distal UCD such as citrullinemia (argininosuccinate synthetase deficiency; (ASSD) and argininosuccinic aciduria (argininosuccinate lyase deficiency); (ASLD) cognitive impairment and neuropsychiatric disease are common even in the absence of acute HA. As a consequence, both citrulline and argininosuccinate (ASA) or their metabolic products have been implicated as neurotoxic. In this project the investigators will use state-of- the-art neuroimaging and neuropsychological methods to investigate whether patients with OTCD have chronically elevated brain Gln and reduced myo-inositol (mI) levels that correlate with regional brain structural abnormalities and neurocognitive dysfunction. The researchers will further investigate whether during an acute episode of HA elevated brain Gln and decreased mI levels correlate with the magnitude of cytotoxic edema and whether a Gln/mI ratio threshold can be identified at which the cytotoxic edema is followed by cell loss. Finally, the researchers will investigate whether regions of brain damage in ASSD and/or ASLD are distinct from those in OTCD and compare brain Gln levels in ASSD and ASLD in the absence of HA to those in OTCD. The investigators will also seek to determine if brain citrulline and ASA can be identified in the brains of patients with distal UCD and whether they correlate with brain abnormalities seen in MRI and neuropsychological testing. This project will elucidate the chronology of brain pathology both in acute hyperammonemia and chronic UCD and whether, proximal and distal UCD differ in their pathophysiology of brain damage.
Detailed description
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.
This study will be separated into three sections. The first study will study longitudinal changes in OTCD. The second section will study the recovery of OTCD participants from a hyperammonemic episode over time. The third section will be a longitudinal study of the distal urea cycle disorders. In all cases, participants in this study will attend an initial study visit that will include a review of medical history, current symptoms, impairments, and diet history; 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 1-2-day period. This will include standard MRI studies and four sessions consisting of functional MRI (fMRI) (CNMC only), 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 multiple time point participation. The study will be conducted at Children's National Medical Center and Boston Children's Hospital.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| OTCD participants | – | Procedure: MRI, Behavioral: BehavioralFemale carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD who can undergo MRI and behavioral testing |
| Normal controls | – | Procedure: MRI, Behavioral: BehavioralHealthy males or females without known medical or metabolic disorder (control group) who can undergo MRI and behavioral testing |
| HA recovery group | – | Procedure: MRI, Behavioral: BehavioralFemale carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD or participants with CPS-1 who have had a recent hyperammonemic episode who can undergo MRI and behavioral testing |
| Distal UCD | – | Procedure: MRI, Behavioral: BehavioralMales and females with ASSD and ASLD who can undergo MRI and behavioral testing |
Who may qualify
- Ages
- 7 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Participants have a urea cycle disorder or are healthy controls ages 7-30 years, male and female. Participants who have had a recent hyperammonemic episode are eligible for a more detailed analysis.
Key inclusion criteria (16 listed)
- Confirmed diagnosis of ornithine transcarbamylase deficiency (OTCD) by genetic analysis (genotype) and/or enzyme analysis with at least a single episode of HA hyperammonemic (HA) encephalopathy
- Ability to undergo MRI without sedation
- Ages 7 - 50 years
- Ability to provide informed consent or assent to the procedures
- Healthy controls (age and gender matched)
Key exclusion criteria (18 listed)
- Inability to undergo MRI without sedation
- Metal implants, including orthodontic braces
- Other health conditions contra-indicated in MRI
- Medically unstable at time of scheduled research visit
- Unable to provide informed consent or assent to the procedures
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRIMRI, fMRI, 1H MRS, DTI | Procedure or surgery | Distal UCD, HA recovery group, Normal controls, OTCD participants |
| BehavioralAlso: cognitive testing, Neuropsychological testingBattery of executive function tasks | Behavioural | Distal UCD, HA recovery group, Normal controls, OTCD participants |
Primary outcome
Change in Concentration of Glutamine and Myoinositol by MRS
Time frame: baseline and 2year follow up
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 protocols used 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).
Change in Fractional Anisotropy
Time frame: baseline and 2 year follow up
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.
1 secondary outcome
Change in behavioral testing results
Time frame: baseline and 2 year follow up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2024.
- Results publication: PubMed 26067829Pacheco-Colon I, Washington SD, Sprouse C, Helman G, Gropman AL, VanMeter JW. Reduced Functional Connectivity of Default Mode and Set-Maintenance Networks in Ornithine Transcarbamylase Deficiency. PLoS One. 2015 Jun 11;10(6):e0129595. doi: 10.1371/journal.pone.0129595. eCollection 2015.
- Results publication: PubMed 24881970Sprouse C, King J, Helman G, Pacheco-Colon I, Shattuck K, Breeden A, Seltzer R, VanMeter JW, Gropman AL. Investigating neurological deficits in carriers and affected patients with ornithine transcarbamylase deficiency. Mol Genet Metab. 2014 Sep-Oct;113(1-2):136-41. doi: 10.1016/j.ymgme.2014.05.007. Epub 2014 May 20.
- Results publication: PubMed 22110002Gropman 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.
- Results publication: PubMed 20488904Gropman 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.
- Results publication: PubMed 20004862Oldham 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.
- Results publication: PubMed 18662894Gropman 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.
- Results publication: PubMed 27132782Shapiro E, Bernstein J, Adams HR, Barbier AJ, Buracchio T, Como P, Delaney KA, Eichler F, Goldsmith JC, Hogan M, Kovacs S, Mink JW, Odenkirchen J, Parisi MA, Skrinar A, Waisbren SE, Mulberg AE. Neurocognitive clinical outcome assessments for inborn errors of metabolism and other rare conditions. Mol Genet Metab. 2016 Jun;118(2):65-9. doi: 10.1016/j.ymgme.2016.04.006. Epub 2016 Apr 14.
- Results publication: PubMed 25712381Waisbren SE, He J, McCarter R. Assessing Psychological Functioning in Metabolic Disorders: Validation of the Adaptive Behavior Assessment System, Second Edition (ABAS-II), and the Behavior Rating Inventory of Executive Function (BRIEF) for Identification of Individuals at Risk. JIMD Rep. 2015;21:35-43. doi: 10.1007/8904_2014_373. Epub 2015 Feb 25.
- Results publication: PubMed 20188616Seminara J, Tuchman M, Krivitzky L, Krischer J, Lee HS, Lemons C, Baumgartner M, Cederbaum S, Diaz GA, Feigenbaum A, Gallagher RC, Harding CO, Kerr DS, Lanpher B, Lee B, Lichter-Konecki U, McCandless SE, Merritt JL, Oster-Granite ML, Seashore MR, Stricker T, Summar M, Waisbren S, Yudkoff M, Batshaw ML. Establishing a consortium for the study of rare diseases: The Urea Cycle Disorders Consortium. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S97-105. doi: 10.1016/j.ymgme.2010.01.014. Epub 2010 Feb 10.
- Results publication: PubMed 12736767Jan W, Zimmerman RA, Wang ZJ, Berry GT, Kaplan PB, Kaye EM. MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation. Neuroradiology. 2003 Jun;45(6):393-9. doi: 10.1007/s00234-003-0955-7. Epub 2003 May 8.
- Individual participant dataSharing planned: Yes. Data will be kept on UCD website and released after study completion
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea L. Gropman, M.D. contact
Andrea L. Gropman, M.D. principal investigator
Children's National Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Urea Cycle Disorders, run by Children's National Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Andrea L Gropman, M.D. (202-476-3511, agropman@childrensnational.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Concentration of Glutamine and Myoinositol by MRS (time frame: baseline and 2year follow up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02935283, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2024.