Urea Cycle DisordersNCT02740153
PCORI Urea Cycle Disorder Study
An observational study of Urea Cycle Disorders, run by Children's National Research Institute at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages Up to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Urea Cycle Disorders
- How many people
- 187 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Mar 2016to 30 Jun 2020
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
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.
Who may be able to join
- 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
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- 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
Who cannot join
- Aim 1:
- Rare and unrelated comorbidities (e.g., Down's syndrome, intraventricular hemorrhage in the newborn period, and extreme prematurity)
Trial locations and contacts
1 site in 1 country.
United States1 site
Childrens Research Institute
Washington D.C., District of Columbia, 20010
About this study
Official title: Comparative Effectiveness of Therapy in Rare Diseases: Liver Transplantation vs. Conservative Management of Urea Cycle Disorders
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.
Read more
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.
Read the detailed 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:
- What is the disease's risk of mortality and illness in the two treatment approaches?
- What can parents expect in terms of the development of their child and his/her school performance?
- 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.
- Conditions
- Urea Cycle Disorders
- Being tested
- No Intervention Given
- Medical subject headings
- Urea Cycle Disorders, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No Intervention GivenOther
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Other: No Intervention Given |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: 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
Measured: Quality of life testing was conducted and reported at baseline for each patient during the study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2016 (estimated)
- Study start4 Mar 2016
- Primary completion10 Jun 2019
- Study completion30 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Urea Cycle DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 187 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's National Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Center for Advancing Translational Sciences (NCATS), Patient-Centered Outcomes Research Institute, George Washington University, The National Urea Cycle Disorders Foundation, Studies of Pediatric Liver Transplantation
- Responsible party
- Principal investigator, Nicholas Ah Mew, Children's National Research Institute
- Investigators
- Mendel Tuchman, MD, Study chair, Children's National Research InstituteNicholas Ah Mew, MD, Principal investigator, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02740153
- Sponsor's protocol ID
- 7282
- Status last verified
- Jan 2021
- First submitted
- 29 Mar 2016
- Last updated
- 26 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Effectiveness of Therapy in Rare Diseases: Liver Transplantation vs. Conservative Management of Urea Cycle Disorders
- ClinicalTrials.gov ID
- NCT02740153
- Acronym / sponsor ID
- 7282
- Conditions
- Urea Cycle Disorders
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 187 participants (actual)
- Lead sponsor
- Children's National Research InstituteUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Center for Advancing Translational Sciences (NCATS), Patient-Centered Outcomes Research Institute, George Washington University, The National Urea Cycle Disorders Foundation, Studies of Pediatric Liver Transplantation
- Study start
- 4 Mar 2016 (actual)
- Primary completion
- 10 Jun 2019 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 15 Apr 2016 (estimated)
- Results
- Posted 26 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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:
- What is the disease's risk of mortality and illness in the two treatment approaches?
- What can parents expect in terms of the development of their child and his/her school performance?
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Urea Cycle Disorder with Liver Transplant | – | Other: No Intervention Given* Age 18 and under * Diagnosed with the following Neonatal-type urea cycle disorders: CPSD, OTCD, ASD or ALD * History of liver transplant |
| Urea Cycle Disorder without Transplant | – | Other: No Intervention Given* 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 |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (10 listed)
- Age 18 and under
- Diagnosed with the following Neonatal-type urea cycle disorders:
- CPSD, OTCD, ASD or ALD, as defined as follows:
- Willing to participate in at least 1 neurocognitive assessment and 1 quality of life assessment
- Permit access to medical records and medical providers
Key exclusion criteria (2 listed)
- Rare and unrelated comorbidities (e.g., Down's syndrome, intraventricular hemorrhage in the newborn period, and extreme prematurity)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No Intervention Given | Other | Urea Cycle Disorder with Liver Transplant, Urea Cycle Disorder without Transplant |
Primary outcome
Mortality
Time frame: 436 person years in the Liver Transplant Group and 386 person-years in the Without Transplant Group
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.
Neurocognitive Function: Full-Scale IQ
Time frame: Neuropsychological testing was conducted once for each patient at baseline during the study on age-matched norms for the specific test used.
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)
Total Quality of Life
Time frame: Quality of life testing was conducted and reported at baseline for each patient during the study.
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mendel Tuchman, MD study chair
Children's National Research Institute
Nicholas Ah Mew, MD principal investigator
Children's National Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Urea Cycle Disorders, run by Children's National Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality (time frame: 436 person years in the Liver Transplant Group and 386 person-years in the Without Transplant Group). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2021.