Neurologic Injuries in Adults With Urea Cycle Disorders

NCT00472732 | Completed Results DMC

• 2 other identifiers: RDCRN 5104U54RR019453
• Study Type: observational
• Target: 46
• Locations: 1 country
• Sites: 2

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.

Conditions

Brain Diseases, Metabolic, Inborn; Urea Cycle Disorder; Ornithine Transcarbamylase Deficiency

Keywords

UCD; OTCD; Ammonia; Urea Metabolism; Inborn Errors

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

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)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD

You may qualify if:

• 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.
• No known medical or metabolic disorder
• IQ of at least 80
• Willing to travel to study site
• English-speaking
• Age between 18 and 60 years

You may not qualify if:

• 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

Sponsors & Collaborators

• Andrea Gropman: lead
• Office of Rare Diseases (ORD): collaborator
• Rare Diseases Clinical Research Network: collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (2)

George Washington University School of Medicine

Washington D.C., District of Columbia, 20037, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

Related Publications (3)

• 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.

  PMID: 14705115 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.

  PMID: 12536032 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.

  PMID: 10946359 BACKGROUND

MeSH Terms

Conditions

Brain Diseases, Metabolic, Inborn; Urea Cycle Disorders, Inborn; Ornithine Carbamoyltransferase Deficiency Disease

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Amino Acid Metabolism, Inborn Errors; Genetic Diseases, X-Linked

Limitations and Caveats

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.

Results Point of Contact

• Title: Andrea Gropman, M.D.
• Organization: Children's Research Institute

agropman@childrensnational.org

202-476-2120

Study Officials

• Andrea Gropman, MD

  Children's National Research Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 11, 2007
• First Posted: May 14, 2007
• Study Start: March 1, 2007
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2010
• Last Updated: June 24, 2015
• Results First Posted: May 29, 2015

Record last verified: 2015-05

Locations

US (2)