PCORI Urea Cycle Disorder Study

NCT02740153 | Completed Results DMC

• 1 other identifier: 7282
• Study Type: observational
• Target: 187
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Urea Cycle Disorders

Outcome Measures

Primary Outcomes (3)

• 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

• 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.

• 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.

Study Arms (2)

Urea Cycle Disorder with Liver Transplant

* Age 18 and under * Diagnosed with the following Neonatal-type urea cycle disorders: CPSD, OTCD, ASD or ALD * History of liver transplant

Other: No Intervention Given

Urea Cycle Disorder without Transplant

* Age 18 and under * Diagnosed with the following Neonatal-type urea cycle disorders: CPSD, OTCD, ASD or ALD * No history of liver transplant, managed medically

Other: No Intervention Given

Interventions

No Intervention Given OTHER

Urea Cycle Disorder with Liver Transplant; Urea Cycle Disorder without Transplant

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

The study population for Aim 1 includes children aged 18 and younger who are diagnosed with one of the following Neonatal-type urea cycle disorders: CPSD, OTCD, ASD, or ALD. Participants will come from children's hospitals and pediatric clinics that treat urea cycle disorders throughout the country.

You may qualify if:

• 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

You may not qualify if:

• Aim 1:
• Rare and unrelated comorbidities (e.g., Down's syndrome, intraventricular hemorrhage in the newborn period, and extreme prematurity)

Sponsors & Collaborators

• Children's National Research Institute: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• Patient-Centered Outcomes Research Institute: collaborator
• George Washington University: collaborator
• The National Urea Cycle Disorders Foundation: collaborator
• Studies of Pediatric Liver Transplantation: collaborator

Study Sites (1)

Childrens Research Institute

Washington D.C., District of Columbia, 20010, United States

Location

MeSH Terms

Conditions

Urea Cycle Disorders, Inborn

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Dr. Nicholas Ah Mew
• Organization: Children's National Medical Center

nahmew@childrensnational.org

202-476-5863

Study Officials

• Mendel Tuchman, MD

  Children's National Research Institute

  STUDY CHAIR

• Nicholas Ah Mew, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 29, 2016
• First Posted: April 15, 2016
• Study Start: March 4, 2016
• Primary Completion: June 10, 2019
• Study Completion: June 30, 2020
• Last Updated: January 26, 2021
• Results First Posted: January 26, 2021

Record last verified: 2021-01

Locations

US (1)