Urea Cycle Disorders Clinical Trial
Official title:
Comparative Effectiveness of Therapy in Rare Diseases: Liver Transplantation vs. Conservative Management of Urea Cycle Disorders
NCT number | NCT02740153 |
Other study ID # | 7282 |
Secondary ID | |
Status | Completed |
Phase | |
First received | |
Last updated | |
Start date | March 4, 2016 |
Est. completion date | June 30, 2020 |
Verified date | January 2021 |
Source | Children's National Research Institute |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
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.
Status | Completed |
Enrollment | 187 |
Est. completion date | June 30, 2020 |
Est. primary completion date | June 10, 2019 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | N/A to 18 Years |
Eligibility | 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) |
Country | Name | City | State |
---|---|---|---|
United States | Childrens Research Institute | Washington | District of Columbia |
Lead Sponsor | Collaborator |
---|---|
Children's National Research Institute | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), George Washington University, National Center for Advancing Translational Science (NCATS), Patient-Centered Outcomes Research Institute, Studies of Pediatric Liver Transplantation, The National Urea Cycle Disorders Foundation |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Mortality | This aspect of Aim 1 is prospective by design based on selection by exposure (liver transplant or medical managed) evaluating the clinical outcomes of subjects with urea cycle disorders. | 436 person years in the Liver Transplant Group and 386 person-years in the Without Transplant Group | |
Primary | Neurocognitive Function: Full-Scale IQ | Neuropsychological tests were based on age-matched norms for the specific test used. All neurocognitive scores have been standardized to the following: norm, mean of 100, and sd of 15. In all tests higher scores are interpreted as higher functions. The WPPSI and WASI were combined to create a single measure of Full-Scale IQ.
Full-Scale IQ Wechsler Preschool and Primary Scales of Intelligence, 4th edition (WPPSI-IV: Children 3-5 years of age) Wechsler Abbreviated Scales of Intelligence, 1st and 2nd editions (WASI-I & II: Persons 6+ years of age) |
Neuropsychological testing was conducted once for each patient at baseline during the study on age-matched norms for the specific test used. | |
Primary | Total Quality of Life | Quality of life assessments are self-reported by participating patients or by their parent/caretaker using the following reports:
Pediatric Family Impact (PedsQL), Version 4 is reported as a total score All were scored on a 0-100 scale. Higher scores indicated a better health-related quality of life |
Quality of life testing was conducted and reported at baseline for each patient during the study. |
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