Comparative Effectiveness of Treatment in Rare Diseases: Liver Transplantation vs. Medical Treatment in Urea Cycle Disorders
Study of Treatment Options for UCD - Liver Transplant vs Standard of Care
This study received funding from the Patient-Centered Outcomes Research Institute (PCORI) to evaluate treatment options and impact on quality of life for patients with urea cycle disorders (UCD). The study is entitled "Comparative Effectiveness of Treatment in Rare Diseases: Liver Transplantation vs. Medical Treatment in Urea Cycle Disorders." Urea cycle disorders are genetic disorders caused by the deficiency of urea cycle enzymes in the liver that are responsible for detoxifying ammonia, a byproduct of metabolizing proteins. The liver’s inability to detoxify ammonia results in accumulation of ammonia in the blood that 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.
Why was this study needed?
"NUCDF proposed this study to answer the critical questions our UCD families face when considering whether to seek liver transplant or continue with standard UCD treatment. Is quality of life improved? What are the risks of transplant compared to the risks of urea cycle disorder? Does transplant make it possible for children to avoid neurological damage associated with UCD?" said Cynthia Le Mons, Executive Director of NUCDF and Co-Principal Investigator of the NIH-funded Rare Diseases Clinical Research Network Urea Cycle Disorders Consortium. "Our UCD families and patients were the center of this important study - their experiences and viewpoints will drive and inform the study. We asked families and their metabolic teams how they reach decisions together about which option is best for the patient. Transplant families reported their experiences with UCD before transplant, their quality of life after transplant, and what factors they considered when making the decision to transplant. Families who are considering transplant or who have decided to continue with standard UCD treatments also reported their unique experiences." The NUCDF and its Patient-Powered Research Team (PPRT) collaborated with clinical investigators to design this study and to ensure that the study sought to answer the questions that are most important to patients and their families. The study collected and analyzed data that including survival rates, neurocognitive function, and quality of life for both treatment groups. This patient-centered approach enabled investigators to gather important information about how families and their providers make treatment decisions currently, and what knowledge gaps exist. 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 to help them make informed decisions about the best treatment option for their children.
Study Details and Research Team
Mendel Tuchman, MD, Chief Research Officer, Children’s National Medical Center, Scientific Director of Children’s Research Institute, and the Mary Elizabeth McGehee Joyce Professor of Pediatrics, the George Washington University School of Medicine, was the Principal Investigator of the study. Dr. Tuchman led a team of investigators from the National Urea Cycle Disorders Foundation (NUCDF), the George Washington University (GW), and the Studies of Pediatric Liver Transplantation (SPLIT). Investigators from the Milken Institute School of Public Health at GW conducted interviews and focus groups of patients, families and their providers with the support of the National Urea Cycle Disorders Foundation (NUCDF). The study utilized data from the NIH-funded Longitudinal Study of Urea Cycle Disorders. The Longitudinal Study has been conducted for more than 10 years by 14 clinical research sites of the Urea Cycle Disorders Consortium. "An increasing number of patients with UCD are undergoing liver transplants," said Dr. Tuchman. Liver transplantation eliminates the ammonia problem and risk of death or ongoing brain injury from UCD, but it does have the risks of post-surgical complications and long-term immunosuppression. Although liver transplant for UCD carries a high success and survival rate, there is a risk of death, just as in standard care for urea cycle disorders. Although conservative medical management using ammonia scavengers helps control ammonia levels, there is always the risk that a metabolic crisis will be triggered by a virus or infection or not complying scrupulously with the UCD diet.
“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 transplantation or continuation of conventional care,” said Dr. Tuchman.
This study was selected for PCORI (Patient-Centered Outcome Research Institute) 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.
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.
Questions and Information
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Study Summary Comparative Effectiveness of UCD Treatments - Liver Transplant vs Standard of Care for Urea Cycle Disorders
Details: Families who participated in the study helped researchers learn the following for each treatment approach:
- Risk of mortality and illness.
- Neurocognitive and developmental outcome.
- Effects on short and long-term quality of life.
- Factors families consider when making the decision to pursue liver trans-plantation or continue with standard therapies for their child with UCD.
To obtain a copy of "Making the Choice - Medical Management or Liver Transplant, the Family Perspective" or for more information about the study, liver transplant for UCD, or to network with other UCD liver transplant families, please contact NUCDF at firstname.lastname@example.org, or call us at (626)578-0833.
“I have been a participant or observer in many efforts to bring together families and researchers in regard to a specific disorder or group of disorders, and I have never seen one in which there was such a superb collaboration and focus on the common goal.”
Hugo Moser, M.D., Adrenoleukodystrophy Researcher (“Lorenzo’s Oil”), Kennedy-Krieger Institute, NIH Monitor to UCDC (In Memoriam)