Neurologic Injuries in Adults With Urea Cycle Disorders

NCT ID: NCT00472732

Last Updated: 2015-06-24

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 46 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2010-07-31

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.

Conditions

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

1

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

No interventions assigned to this group

2

Healthy males or females without known medical or metabolic disorder (control group)

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Office of Rare Diseases (ORD)

NIH

Sponsor Role: collaborator

Rare Diseases Clinical Research Network

NETWORK

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

Andrea Gropman

OTHER

Sponsor Role: lead

Responsible Party

Andrea Gropman

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Andrea Gropman, MD

Role: STUDY_CHAIR

Children's National Research Institute

Locations

George Washington University School of Medicine

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

Georgetown University

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

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 14705115 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12536032 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10946359 (View on PubMed)

Other Identifiers

U54RR019453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

RDCRN 5104

Identifier Type: -

Identifier Source: org_study_id