Actively Recruiting

Age: 7Years - 50Years
All Genders
Healthy Volunteers
ID02935283

Neuroimaging and Neuropsychological Outcomes in Urea Cycle Disorders

Led by Children's National Research Institute · Updated on 2024-06-25

56

Participants Needed

1

Research Sites

21 weeks

Total Duration

On this page

Sponsors

C

Children's National Research Institute

Lead Sponsor

B

Boston Children's Hospital

Collaborating Sponsor

AI-Summary

What this Trial Is About

Urea cycle disorders (UCDs) are rare genetic conditions affecting how the body removes ammonia, a waste from protein breakdown. This research focuses on ornithine transcarbamylase deficiency (OTCD), the most common type, and other related disorders such as argininosuccinate synthetase deficiency (ASSD) and argininosuccinate lyase deficiency (ASLD). The study aims to understand brain changes and cognitive effects linked to these disorders by comparing brain chemical levels and structural abnormalities using advanced imaging and neuropsychological testing. The study includes three parts: a longitudinal study of OTCD, a recovery study after hyperammonemic episodes, and a longitudinal study of distal UCDs like ASSD and ASLD. Participants will undergo various brain imaging methods including standard MRI, functional MRI, diffusion tensor imaging, and magnetic resonance spectroscopy to assess brain chemistry and structure. Behavioral and cognitive tests will be performed alongside imaging during initial and follow-up visits. Participants will attend initial visits involving medical history reviews, neurological exams, and cognitive and motor testing over one to two days. They will undergo multiple imaging sessions while performing tasks during functional MRI. Researchers will measure changes in brain glutamine and myo-inositol levels and fractional anisotropy over two years, alongside behavioral outcomes. The study includes safety monitoring and aims to clarify brain damage progression in different UCD types.

CONDITIONS

Brief Title

Neuroimaging and Neuropsychological Outcomes in Urea Cycle Disorders

Who Can Participate

Age: 7Years - 50Years
All Genders
Healthy Volunteers

Eligibility Criteria

Eligible

You may qualify if you...

  • Confirmed diagnosis of ornithine transcarbamylase deficiency (OTCD) by genetic or enzyme analysis with at least one hyperammonemic episode
  • Ability to undergo MRI without sedation
  • Age between 7 and 50 years
  • Ability to provide informed consent or assent
  • Healthy controls matched by age and gender
  • Males and females with a UCD experiencing an acute metabolic crisis with ammonia levels between 100-300 µM
  • Participants must be awake, medically stable, and able to maintain airway during imaging
  • Age between 7 and 30 years for acute metabolic crisis group
  • Sexually active females must agree to urine pregnancy test
  • Confirmed diagnosis of argininosuccinate synthetase deficiency (ASSD) or argininosuccinate lyase deficiency (ASLD) by genetic or enzyme analysis
  • Ability to undergo MRI without sedation
  • Age between 7 and 30 years
  • Ability to provide informed consent or assent
Not Eligible

You will not qualify if you...

  • Inability to undergo MRI without sedation
  • Metal implants including orthodontic braces
  • Other health conditions contraindicating MRI
  • Medically unstable at time of research visit
  • Unable to provide informed consent or assent
  • Ammonia levels outside 100-300 µM for acute metabolic crisis group
  • Presence of coma or inability to maintain airway
  • Age below 7 or above 30 years for acute metabolic crisis group
  • Presence of ferromagnetic devices unsafe for MRI
  • Pregnancy
  • Medically unstable or at risk for decompensation
  • Combative or severely neurologically compromised participants
  • Declining medical status during imaging

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Diagnostic Evaluation

Duration - 1 to 2 days

Participants attend an initial study visit including medical history review, neurological and physical exams, and cognitive and motor testing. Participants also undergo multiple MRI scans including standard MRI, functional MRI, diffusion tensor imaging, and magnetic resonance spectroscopy to assess brain metabolism and structure.

1 to 2 visits (in-person)

Long-term Monitoring

Duration - Up to 2 years

Participants return for follow-up assessments to study longitudinal changes or recovery after hyperammonemic episodes. This includes repeated cognitive and behavioral testing and MRI scans to monitor changes over time.

Follow-up visits at baseline and 2-year time points

Trial Site Locations

Total: 1 location

1

Children's Research Institute

Washington D.C., District of Columbia, United States, 20010

Actively Recruiting

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Research Team

A

Andrea L Gropman, M.D.

A

Andrea L. Gropman, M.D.

How is the study designed?

Study Type

OBSERVATIONAL

Masking

N/A

Allocation

N/A

Model

N/A

Primary Purpose

N/A

Number of Arms

4

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Published Research Related To This Trial

Reduced Functional Connectivity of Default Mode and Set-Maintenance Networks in Ornithine Transcarbamylase Deficiency.

Ileana Pacheco-Colón, Stuart D Washington, Courtney Sprouse...

https://pubmed.ncbi.nlm.nih.gov/26067829

Diffusion tensor imaging detects areas of abnormal white matter microstructure in patients with partial ornithine transcarbamylase deficiency.

A L Gropman, B Gertz, K Shattuck...

https://pubmed.ncbi.nlm.nih.gov/20488904

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.

Susan E Waisbren, Jianping He, Robert McCarter

https://pubmed.ncbi.nlm.nih.gov/25712381