Investigating brain function in urea cycle disorders

Neuroimaging and Neuropsychological Outcomes in Urea Cycle Disorders

This study is trying to understand how urea cycle disorders, especially ornithine transcarbamylase deficiency, affect brain function and thinking skills in patients.

Quick facts

• Study type: Observational
• Enrollment: 56 (estimated)
• Ages: 7 Years to 50 Years
• Sex: All
• Sponsor: Children's National Research Institute (Academic / other)
• Locations: 1 site (Washington D.C., District of Columbia)
• Trial ID: NCT02935283 on ClinicalTrials.gov

What this trial studies

This observational study focuses on understanding the neurological impacts of urea cycle disorders (UCD), particularly ornithine transcarbamylase deficiency (OTCD). Researchers will utilize advanced neuroimaging techniques and neuropsychological assessments to evaluate brain metabolism and cognitive function in patients with OTCD and other UCDs. The study will be divided into three sections, examining longitudinal changes in OTCD, recovery from hyperammonemic episodes, and the effects of distal UCDs. Participants will undergo comprehensive evaluations, including medical history reviews, neurological exams, and cognitive testing.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 7-50 with a confirmed diagnosis of ornithine transcarbamylase deficiency and a history of hyperammonemic encephalopathy.

Not a fit: Patients with other forms of urea cycle disorders who do not meet the inclusion criteria or those unable to undergo MRI safely may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and management of neurological complications in patients with urea cycle disorders.

How similar studies have performed: While there have been studies on urea cycle disorders, this specific approach using advanced neuroimaging techniques is relatively novel.

Eligibility criteria

Inclusion Criteria:

Inclusion criteria for group 1:

1. 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
2. Ability to undergo MRI without sedation
3. Ages 7 - 50 years
4. Ability to provide informed consent or assent to the procedures
5. Healthy controls (age and gender matched)

Inclusion criteria for group 2:

1. Males and females with a UCD who are having an acute metabolic crisis, with ammonia levels between 100-300 µM
2. 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
3. Age range 7-30 years
4. Able to undergo neuroimaging safely (i.e. without ferromagnetic devices)
5. Sexually active female of childbearing potential must agree to urine pregnancy test
6. Admitted to the hospital for treatment of HA at one of the 4 sites for this study
7. Can be subjects who were originally enrolled in aim 1 who then have HA (they will cross over to aim 2)

Inclusion criteria for group 3

1. Confirmed diagnosis of arginosuccinate ASSD, and ASLD by genotype and/or enzyme analysis or healthy age and gender matched control
2. Ability to undergo MRI without sedation
3. Age 7 - 30 years
4. Able to provide informed consent or assent to the procedures

Exclusion Criteria:

Exclusion Criteria for group 1:

1. Inability to undergo MRI without sedation
2. Metal implants, including orthodontic braces
3. Other health conditions contra-indicated in MRI
4. Medically unstable at time of scheduled research visit
5. Unable to provide informed consent or assent to the procedures

Exclusion criteria for group 2:

1. Ammonia level \> 300 µM, or \<100 µM
2. Presence of coma and/or inability to maintain a patent airway
3. Age \<7 or \>30 years
4. Subject with ferromagnetic device that precludes safe MRI imaging
5. Pregnant female
6. Unstable medically, at risk for decompensations
7. 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

Exclusion criteria for group 3:

1. Inability to undergo MRI without sedation
2. Metal implants, including orthodontic braces
3. Other health conditions contra-indicated for MRI
4. Medically unstable at time of scheduled research visit
5. Unable to provide informed consent or assent

Where this trial is running

Washington D.C., District of Columbia

• Children's Research Institute — Washington D.C., District of Columbia, United States (Recruiting)

Study contacts

• Principal investigator: Andrea L. Gropman, M.D. — Children's National Research Institute
• Study coordinator: Andrea L Gropman, M.D.

Conditions Urea Cycle Disorders