PCORI Urea Cycle Disorder Study

Urea Cycle Disorders Clinical Trial

Official title: Comparative Effectiveness of Therapy in Rare Diseases: Liver Transplantation vs. Conservative Management of Urea Cycle Disorders

Status Completed

Clinical Trial 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.

Clinical Trial Description

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 involves a special diet low in protein, drugs that help metabolize ammonia and amino acid supplements (conservative management). Many patients and families choose liver transplantation rather than conservative treatment; both alternatives are effective in reducing or normalizing blood ammonia. While liver transplantation eliminates the ammonia problem, conservative management does so only temporarily and in many patients, blood ammonia can rise during an infection.

The long-term objective of this study is to help patients make decisions about management alternatives (conservative vs. liver transplantation) by providing them with scientific information that is currently lacking. The questions the investigators will address are:

1. What is the disease's risk of mortality and illness in the two treatment approaches?

2. What can parents expect in terms of the development of their child and his/her school performance?

3. What are the expected effects of each treatment on short-term and long-term quality of life?

The investigators will use statistical methods to compare numbers or percentages of survival, illness, psychological testing for IQ, executive function, memory, behaviors, and quality of life among patients that choose conservative management and those who have chosen liver transplantation. Some of this information is already being collected by the Urea Cycle Disorders Consortium (UCDC) in 14 metabolic clinics (11 of them in the US) as part of its long-term follow-up study. To ensure that the information the investigators analyze is representative of the UCD patient population in the US, the investigators will also obtain data from the Studies of Pediatric Liver Transplantation (SPLIT) registry, which collects information about children who undergo liver transplantation for many different diseases (including UCD).

The National Urea Cycle Disorders Foundation (NUCDF) and the Patients' Research Working Group collaborated with the clinical investigators to design this research and to ensure that it that it covers the questions that are most important to patients and their families. The results of this study will be disseminated to patients, their doctors, and clinical staff so they receive current, validated information before making a decision about the best treatment for them. ;

Related Conditions & MeSH terms

• Urea Cycle Disorders
• Urea Cycle Disorders, Inborn

• NCT number: NCT02740153
• Study type: Observational
• Source: Children's National Research Institute
• Status: Completed
• Start date: March 4, 2016
• Completion date: June 30, 2020