Recruiting

Observational StudyLongitudinal Study of Urea Cycle Disorders

Sponsor:

Andrea Gropman

Code:

NCT00237315

Conditions

Brain Diseases, Metabolic, Inborn

Amino Acid Metabolism, Inborn Errors

Urea Cycle Disorders

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Study Details

Brief summary:

Urea cycle disorders (UCD) are a group of rare inherited metabolism disorders. Infants and children with UCD commonly experience episodes of vomiting, lethargy, and coma. The purpose of this study is to perform a long-term analysis of a large group of individuals with various UCDs. The study will focus on the natural history, disease progression, treatment, and outcome of individuals with UCD.

Conditions

Brain Diseases, Metabolic, Inborn

Amino Acid Metabolism, Inborn Errors

Urea Cycle Disorders

Study ID

NCT00237315

Start date

Feb, 2006

Status verified date

Feb, 2024

Completion date

Jul, 2026

Anticipated

Primary completion date

Jul, 2025

Anticipated

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

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)

Study Design

Enrollment

1500 participants

Anticipated

Interventions and Outcome Measures

Primary outcome measure

Prevalence of specific morbid indicators of disease severity [ Time Frame: End of study ]
Relationship between various biomarkers and disease severity and progression [ Time Frame: End of study ]
Safety and efficacy of currently used and new UCD therapies [ Time Frame: End of study ]

Central Contacts and Locations

Central contacts

Jennifer Seminara, MPH

202-306-6489 jseminar@childrensnational.org

Locations

University of California, Los Angeles

Recruiting

Los Angeles, California, United States, 90095

Contacts

Julia Sloan

310-794-3374 JSloan@mednet.ucla.edu

Principal Investigator:

Derek Wong, MD

Stanford University Medical Center

Recruiting

Stanford, California, United States, 94305

Contacts

Thu Quan, MBA, HCM

650-736-8166 tquan@stanford.edu

Principal Investigator:

Gregory Enns, MD

Children's Hospital Colorado

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Christien Hernandez

720-777-0440 Christien.Hernandez@childrenscolorado.org

Principal Investigator:

Shawn McCandless, MD

Children's National Medical Center

Recruiting

Washington, District of Columbia, United States, 20010

Contacts

Kara Simpson, MS, CGC

202-476-6216 ksimpson@childrensnational.org

Principal Investigator:

Nicholas Ah Mew, MD

Children's Hospital Boston (UCDC New England Center)

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Debbie Fu

617-919-7631 Yu-Ting.Fu@childrens.harvard.edu

Principal Investigator:

Gerard Berry, MD

University of Minnesota

Recruiting

Minneapolis, Minnesota, United States, 55455

Contacts

Sara Elsbecker, MS, RN, CPNP

612-626-5275 selsbeck10@umphysicians.umn.edu

Principal Investigator:

Susan Berry, MD

Icahn School of Medicine at Mount Sinai

Recruiting

New York, New York, United States, 10029

Contacts

Alison Tiao

212-659-8540 alison.tiao@mssm.edu

Principal Investigator:

Margo Breilyn, MD

Case Western Medical College

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Genya Kisin

216-286-9202 Genya.Kisin@UHhospitals.org

Principal Investigator:

Laura Konczal, MD

Oregon Health and Science University

Recruiting

Portland, Oregon, United States, 97239

Contacts

Ursula Kuhn

503-494-4290 kuhnu@ohsu.edu

Principal Investigator:

Cary Harding, MD

Children's Hospital of Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Mita Majumdar

267-425-5876 majumdarm@chop.edu

Principal Investigator:

Can Ficicioglu, MD

Baylor College of Medicine

Recruiting

Houston, Texas, United States, 77030

Contacts

Saima Ali, RN, FNP-C

832-822-4183 sma1@bcm.edu

Principal Investigator:

Sandesh Nagamani, MD

Children's Hospital and Regional Medical Center

Recruiting

Seattle, Washington, United States, 98105

Contacts

Hayden Vreugdenhil

206-884-1264 Hayden.Vreugdenhil@seattlechildrens.org

Principal Investigator:

Christina Lam, MD, PhD

The Hospital for Sick Children

Recruiting

Toronto, Ontario, Canada, M5G 1X8

Contacts

Liora Caspi

416-813-7654 liora.caspi@sickkids.ca

Principal Investigator:

Andreas Schulze, MD

More Information

Sponsor

Andrea Gropman

Last update posted

Feb 13, 2024

Last verified

Feb, 2024

Keywords

Urea
Inherited metabolic disorders

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Andrea Gropman on 2024-02-13.