Long-term analysis of urea cycle disorders
Longitudinal Study of Urea Cycle Disorders
This study looks at how urea cycle disorders affect people over time to see how the disease progresses and how different treatments work.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 1500 (estimated) |
| Sex | All |
| Sponsor | Children's National Research Institute Academic / other |
| Locations | 15 sites (Los Angeles, California and 14 other locations) |
| Trial ID | NCT00237315 on ClinicalTrials.gov |
What this trial studies
This observational study focuses on individuals with urea cycle disorders (UCDs), which are rare inherited metabolic conditions affecting protein breakdown. The study aims to analyze the natural history, disease progression, treatment outcomes, and cognitive function of patients with various UCDs over an extended period. Participants will undergo initial assessments including medical history, physical exams, psychological testing, and blood tests, followed by regular follow-up visits to monitor their health and biochemical status. The goal is to identify biochemical changes that could predict future metabolic imbalances and improve patient outcomes.
Who should consider this trial
Good fit: Ideal candidates include individuals diagnosed with specific urea cycle disorders such as NAGS deficiency, CPS I deficiency, OTC deficiency, or AS deficiency.
Not a fit: Patients without a confirmed diagnosis of a urea cycle disorder or those with unrelated metabolic conditions may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could lead to better management and treatment strategies for patients with urea cycle disorders.
How similar studies have performed: Other studies on urea cycle disorders have shown promise in understanding disease progression and treatment outcomes, indicating that this approach is supported by previous research.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Diagnosis of NAGS deficiency, defined as the detection of a pathogenic mutation, and/or decreased (less than 20 % of control) NAGS enzyme activity in liver ,and/or hyperammonemia and first degree relative meets at least one of the criteria for NAGS deficiency * 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 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 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 * Diagnosis of ARG deficiency (Hyperargininemia), defined as a greater than or equal to 5-fold elevated arginine levels in the blood, and/or decreased arginase enzyme levels in red blood cells or other appropriate tissue, and/or identification of a pathogenic mutation in the ARG gene, and/or hyperammonemia and first degree relative meets at least one of the criteria for ARG Deficiency * Diagnosis of HHH Syndrome or ORNT deficiency, defined as a greater than or equal to 5-fold elevated plasma ornithine and homocitrulline levels in the urine, and/or a pathogenic mutation, and/or less than 20% residual labeled ornithine incorporation into protein in cultured fibroblasts, and/or hyperammonemia and first degree relative meets at least one of the criteria for HHH Syndrome or ORNT Deficiency * Diagnosis of CITR deficiency (Citrullinemia Type II), defined as elevated citrulline levels in the blood and a pathogenic mutation and/or hyperammonemia and first degree relative meets criteria for CITR Deficiency * Pending diagnosis of a UCD (UCD highly likely), defined as laboratory values highly suggestive of a UCD with symptomatic hyperammonemic episodes but without a verifiable diagnosis Exclusion Criteria: * Hyperammonemia caused by an organic academia, lysinuric protein intolerance, mitochondrial disorder, congenital lactic academia, fatty acid oxidation defects, or primary liver disease * Rare and unrelated comorbidities (e.g., Down's syndrome, intraventricular hemorrhage in the newborn period, and extreme prematurity)
Where this trial is running
Los Angeles, California and 14 other locations
- University of California, Los Angeles — Los Angeles, California, United States (Recruiting)
- Stanford University Medical Center — Stanford, California, United States (Recruiting)
- Children's Hospital Colorado — Aurora, Colorado, United States (Recruiting)
- Children's National Medical Center — Washington D.C., District of Columbia, United States (Recruiting)
- Children's Hospital Boston (UCDC New England Center) — Boston, Massachusetts, United States (Recruiting)
- University of Minnesota — Minneapolis, Minnesota, United States (Recruiting)
- Icahn School of Medicine at Mount Sinai — New York, New York, United States (Recruiting)
- Case Western Medical College — Cleveland, Ohio, United States (Recruiting)
- Oregon Health and Science University — Portland, Oregon, United States (Recruiting)
- Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Recruiting)
- Baylor College of Medicine — Houston, Texas, United States (Recruiting)
- Children's Hospital and Regional Medical Center — Seattle, Washington, United States (Recruiting)
- The Hospital for Sick Children — Toronto, Ontario, Canada (Recruiting)
- University of Heidelberg — Heidelberg, Germany (Recruiting)
- University Children's Hospital — Zurich, Switzerland (Recruiting)
Study contacts
- Study coordinator: Jennifer Seminara, MPH
- Email: jseminar@childrensnational.org
- Phone: 202-306-6489
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.