Neuroimaging and Neuropsychological Outcomes in Urea Cycle Disorders
Nyckelord
Abstrakt
Beskrivning
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.
This study will be separated into three sections. The first study will study longitudinal changes in OTCD. The second section will study the recovery of OTCD participants from a hyperammonemic episode over time. The third section will be a longitudinal study of the distal urea cycle disorders. In all cases, participants in this study will attend an initial study visit that will include a review of medical history, current symptoms, impairments, and diet history; 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 1-2-day period. This will include standard MRI studies and four sessions consisting of functional MRI (fMRI) (CNMC only), 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 multiple time point participation. The study will be conducted at Children's National Medical Center and Boston Children's Hospital.
Datum
| Senast verifierad: | 12/31/2019 |
| Först skickat: | 05/11/2016 |
| Beräknad anmälan inlämnad: | 10/12/2016 |
| Först publicerad: | 10/16/2016 |
| Senaste uppdatering skickad: | 01/20/2020 |
| Senaste uppdatering publicerad: | 01/22/2020 |
| Faktiskt startdatum för studien: | 07/31/2016 |
| Uppskattat primärt slutdatum: | 06/30/2024 |
| Beräknat slutfört datum: | 11/30/2024 |
Tillstånd eller sjukdom
Intervention / behandling
Procedure: MRI
Behavioral: Behavioral
Fas
Armgrupper
| Ärm | Intervention / behandling |
|---|---|
| OTCD participants Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD who can undergo MRI and behavioral testing | |
| Normal controls Healthy males or females without known medical or metabolic disorder (control group) who can undergo MRI and behavioral testing | |
| HA recovery group Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD or participants with CPS-1 who have had a recent hyperammonemic episode who can undergo MRI and behavioral testing | |
| Distal UCD Males and females with ASSD and ASLD who can undergo MRI and behavioral testing |
Urvalskriterier
| Åldrar berättigade till studier | 7 Years Till 7 Years |
| Kön som är berättigade till studier | All |
| Testmetod | Probability Sample |
| Accepterar friska volontärer | Ja |
| Kriterier | 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 |
Resultat
Primära resultatåtgärder
1. Change in Concentration of Glutamine and Myoinositol by MRS [baseline and 2year follow up]
2. Change in Fractional Anisotropy [baseline and 2 year follow up]
Sekundära resultatåtgärder
1. Change in behavioral testing results [baseline and 2 year follow up]
