Clinical trial NCT00472732: Neurologic Injuries in Adults With Urea Cycle Disorders
Official title: Assessing Neural Mechanisms of Injury in Inborn Errors of Urea Metabolism Using Structural MRI, Functional MRI, and Magnetic Resonance Spectroscopy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Brain Diseases, Metabolic, Inborn
Urea Cycle Disorder
Ornithine Transcarbamylase Deficiency
Keywords: UCD
OTCD
Ammonia
Urea Metabolism
Inborn Errors
Lead sponsor: Children's National Research Institute
Sponsor class: OTHER
Collaborators: name: Office of Rare Diseases (ORD)
name: Rare Diseases Clinical Research Network
name: National Center for Research Resources (NCRR)
First posted: 2007-05-14
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD

Brief summary: 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.

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.

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.

Eligibility criteria: Inclusion Criteria for Participants with OTCD:

* Diagnosis of OTCD or heterozygote state of OTCD by metabolic or molecular means. Female participants must be clinically stable and heterozygous for OTCD. Male participants must be hemizygous for late onset OTCD.

Inclusion Criteria for Healthy Controls:

* No known medical or metabolic disorder

Inclusion Criteria for All Participants:

* IQ of at least 80
* Willing to travel to study site
* English-speaking
* Age between 18 and 60 years

Exclusion Criteria for All Participants:

* Currently being treated for an acute illness
* History of neuropsychiatric drug use
* Unable to undergo MRI scanning without being sedated
* Unable to participate in neurocognitive and/or motor testing
* Metal device in body that might interfere with MRI scanning
* Pregnancy or breastfeeding

Primary outcomes:
measure: Concentration of Glutamine and Myoinositol by MRS
timeFrame: one time measurement at study baseline
measure: Functional MRI Activation in N-Back Tast
timeFrame: one time measurement at study baseline
measure: Fractional Anisotropy
timeFrame: one time measurement at study baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: George Washington University School of Medicine
state: District of Columbia
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
Study officials:
affiliation: Children's National Research Institute
name: Andrea Gropman, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.