N/A
N=187
PCORI Urea Cycle Disorder Study
Urea Cycle Disorders
Bottom Line
View on ClinicalTrials.gov: NCT02740153 ↗Enrolled (actual)
187
Serious AEs
0.0%
Results posted
Jan 2021
Primary outcome: Primary: Mortality — 18.4; 20.7 participant per 1000 person-years
Study Design & Population
- Study type
- Observational
- Phase
- N/A
- Interventions
- No Intervention Given (Other)
- Age
- Pediatric, Adult
- Sex
- All
- Sponsor
- Children's National Research Institute
- Primary completion
- Jun 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mortality |
18.4; 20.7 | — |
| PRIMARY Neurocognitive Function: Full-Scale IQ |
80.1; 82 | — |
| PRIMARY Total Quality of Life |
69.8; 55.6 | — |
Summary
Urea cycle disorders (UCD) are genetic disorders caused by the liver's inability to break down ammonia from proteins; ammonia then accumulates and is toxic to the brain. UCD cause brain damage and intellectual and developmental disabilities and even death.
Treatment for UCD is either conservative management which involves a low-in-protein diet, drugs, and amino acid supplements or liver transplantation; each carries their own risks.
This study aims to help patients to make the decision about different management alternatives by providing them with scientific information that is currently lacking.
Aim 1 of this study will compare survival, neurocognitive function, and patient-reported quality of life.
Eligibility Criteria
Inclusion Criteria
Aim 1 (UCD patients):
- Age 18 and under
- Diagnosed with the following Neonatal-type urea cycle disorders:
- CPSD, OTCD, ASD or ALD, as defined as follows:
- Diagnosis of CPS I deficiency, defined as decreased (less than 20 % of control) CPS I enzyme activity in liver, and/or an identified pathogenic mutation, and/or hyperammonemia and first-degree relative meets at least one of the criteria for CPS I deficiency
- Diagnosis of OTC deficiency, defined as the identification of a pathogenic mutation, and/or less than 20% of control of OTC activity in the liver, and/or elevated urinary orotate (greater than 20 uM/mM) in a random urine sample or after allopurinol challenge test, and/or hyperammonemia and first degree relative meets at least one of the criteria for OTC deficiency
- Diagnosis of AS deficiency (Citrullinemia), defined as a greater than or equal to 10-fold elevation of citrulline in plasma, and/or decreased (less than 20% of control) AS enzyme activity in cultured skin fibroblasts or other appropriate tissue, and/or identification of a pathogenic mutation in the AS gene, and/or hyperammonemia and first degree relative meets at least one of the criteria for AS Deficiency
- Diagnosis of AL deficiency (Argininosuccinic Aciduria, ASA), defined as the presence of argininosuccinic acid in the blood or urine, and/or decreased (less than 20% of control) AL enzyme activity in cultured skin fibroblasts or other appropriate tissue, and/or identification of a pathogenic mutation in the AL gene, and/or hyperammonemia and first degree relative meets at least one of the criteria for AL Deficiency
- Willing to participate in at least 1 neurocognitive assessment and 1 quality of life assessment
- Permit access to medical records and medical providers
Exclusion Criteria
Aim 1:
- Rare and unrelated comorbidities (e.g., Down's syndrome, intraventricular hemorrhage in the newborn period, and extreme prematurity)
Data sourced from ClinicalTrials.gov (NCT02740153). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.