Clinical Trial: Longitudinal Study of Urea Cycle Disorders

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Longitudinal Study of Urea Cycle Disorders

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.

Detailed Summary:

Urea cycle disorders are a group of rare genetic diseases that affect how protein is broken down in the body. UCDs are caused by a deficiency in one of six enzymes or two mitochondrial membrane transporters responsible for removing ammonia, a waste product of protein metabolism, from the bloodstream. Normally, ammonia is converted into urea and then removed from the body in the form of urine. In UCDs, however, ammonia accumulates unchecked and is not removed from the body. It then reaches the brain through the blood, where it causes irreversible brain damage and/or death.

All UCDs, except for one (ornithine transcarbamylase deficiency), are inherited as recessive traits. The purpose of this study is to perform a long-term analysis of a large group of individuals with various UCDs. Biochemical status, growth, and cognitive function will be assessed. Survival and cognitive outcome of the two most commonly used forms of treatment, alternate pathway therapy and transplantation, will be evaluated. In addition, this study will identify the biochemical changes that may predict future metabolic imbalances so that they may be corrected before clinical symptoms develop.

This observational study is funded through 2019. All participants will attend an initial study visit, which will include a medical and diet history, physical and neurological examinations, psychological testing, and blood tests. Participants will then be followed with subsequent study visits, which will last 2-3 hours each. Individuals with neonatal onset UCD will be assessed every 3 months until age 2 and every 6 months thereafter. Individuals with late onset UCD will be evaluated every 6 months. Psychological testing will take place every 2 years. Psychological testing will take from 30 minutes (for younger children) up to 3 hours, depending on test battery.


Sponsor: Mendel Tuchman

Current Primary Outcome:

  • Prevalence of specific morbid indicators of disease severity [ Time Frame: End of study ]
    hyperammonemia, developmental disabilities, long-term renal and hepatic effects, and case-fatality associated with the various forms of UCD
  • Relationship between various biomarkers and disease severity and progression [ Time Frame: End of study ]
    correlation between glutamine, ammonia, liver function (biomarkers) and severity scale and IQ in terms of outcome
  • Safety and efficacy of currently used and new UCD therapies [ Time Frame: End of study ]
    Interim events related to treatments (drugs, diet or liver transplant)


Original Primary Outcome:

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Children's Research Institute

Dates:
Date Received: October 10, 2005
Date Started: February 2006
Date Completion: December 2019
Last Updated: July 25, 2016
Last Verified: July 2016