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Children's National Research Team Awarded $2 Million for Urea Cycle Disorders Study

A research team at Children’s National Health System has been approved for a $2.1 million funding award by the Patient-Centered Outcomes Research Institute  (PCORI) to evaluate treatment options and impacts of care delivery for patients with Urea cycle disorders (UCD), rare genetic diseases predominately of childhood. 

Mendel Tuchman, MD, Chief Research Officer, Children’s National and Scientific Director, Children’s Research Institute, and the Mary Elizabeth McGehee Joyce Professor of Pediatrics, the George Washington University School of Medicine, is the Principal Investigator of this study entitled, “Comparative Effectiveness of Treatment in Rare Diseases: Liver transplantation vs. Medical Treatment in Urea Cycle Disorders.” Dr. Tuchman is leading a team of investigators from Children’s National, the George Washington University (GW), the National Urea Cycle Foundation (NUCDF), and the Studies of Pediatric Liver Transplantation (SPLIT). 

The PCORI Board has approved this award pending completion of a business and programmatic review by PCORI staff and issuance of a formal contract. 

“This project was selected for PCORI funding not only for its scientific merit and commitment to engaging patients and other stakeholders, but also for its potential to fill an important gap in our health knowledge and give people information to help them weigh the effectiveness of their care options,” said PCORI Executive Director Joe Selby, MD, MPH. “We look forward to following the study’s progress and working with Children’s National Health System to share the results.”

Urea cycle disorders 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 can result in brain damage, intellectual and developmental disabilities, and even death. The estimated incidence of urea cycle disorders is 1 in 8,500 births. 

“This study will inform families and healthcare providers about outcomes of patients with UCD who underwent liver transplantation, as compared to those who continued with standard medical and nutritional management,” said Dr. Tuchman. “In addition, we will investigate how families and providers together reach decisions on selecting one vs. the other form of treatment.”

An increasing number of patients with UCD are undergoing liver transplants, instead of the conservative treatment, but both options are considered effective in reducing or normalizing blood ammonia levels, Dr. Tuchman said. Although liver transplantation eliminates the ammonia problem, there is risk of post-surgical complications and even death; and while conservative medical management controls ammonia levels, it does so only temporarily with the risk that a metabolic crisis can be instigated by an infection or dietary indiscretion. 

In this study, the team will focus on the currently available major treatment options in UCD to help families make decisions about management alternatives in care. These decisions include whether to continue conservative treatment, which includes a special diet and drugs that help metabolize ammonia and amino acid supplements to permit normal growth, or to choose liver transplantation, a curative treatment but one that carries significant risks. 

The Children’s National study will collect and analyze data that include survival rates, neurocognitive function, and quality of life for both treatment groups, Dr. Tuchman said. 
Investigators from the Milken Institute School of Public Health at GW with the support of the UCD patient advocacy organization, the NUCDF, will conduct interviews and focus groups with patients and/or families and their medical providers to determine the important issues they consider when deciding whether to opt for liver transplantation or to continue conservative treatment, Dr. Tuchman said.

The NUCDF collaborated with clinical investigators to design this study and to ensure that it seeks to answer the questions that are most important to patients and their families.

This study was selected for PCORI funding through a highly competitive review process in which patients, clinicians, and other stakeholders joined clinical scientists to evaluate submitted proposals. Applications were assessed for scientific merit, engagement with patients and other stakeholders, and methodological rigor among other criteria.

The results of the study will be disseminated to UCD patients and families and to health care providers so that families receive current, validated information before making a decision about the best treatment for their children.

PCORI is an independent, nonprofit organization authorized by Congress in 2010 to fund research that will provide patients, their caregivers, and clinicians with the evidence-based information needed to make better-informed healthcare decisions.
“Short and long-term outcomes that are evidence based are sorely needed to allow patients and health care providers to make truly informed decisions about selecting liver transplantations or continuation of conventional care,” said Dr. Tuchman.  “Our study is designed to meet the mission of PCORI.”

Contact: Caitlyn Camacho at 202-476-4500.


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