Neuroimaging and Neuropsychological Outcomes in Urea Cycle Disorders

Launched by CHILDREN'S NATIONAL RESEARCH INSTITUTE · Oct 13, 2016

Keywords

ClinConnect Summary

This clinical trial is studying how certain brain changes may affect people with urea cycle disorders (UCD), specifically focusing on conditions like ornithine transcarbamylase deficiency (OTCD) and other related disorders. The researchers want to understand how high levels of ammonia in the blood, which can happen during a medical crisis, might impact the brain. They are using advanced brain imaging techniques and tests to explore whether patients with OTCD have specific brain changes that could be linked to their symptoms. They are also interested in looking at brain differences between those with OTCD and other types of UCD, even when ammonia levels are not high.

To participate in this trial, potential subjects need to be between the ages of 7 and 50 and have a confirmed diagnosis of OTCD or other related urea cycle disorders. Participants will undergo brain scans (MRIs) to help researchers gather important information about their brain function and structure. The study is currently recruiting participants, and they will be closely monitored to ensure their safety during the scanning process. Overall, this research aims to improve our understanding of how these disorders affect the brain and may help develop better treatment strategies in the future.

Gender

ALL

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