Status:
UNKNOWN
N-Carbamylglutamate (Carbaglu) In The Treatment Of Hyperammonemia
Lead Sponsor:
Mendel Tuchman
Collaborating Sponsors:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Conditions:
Inborn Errors of Metabolism
Eligibility:
All Genders
1-70 years
Phase:
PHASE2
PHASE3
Brief Summary
This study is based on the hypothesis that a new drug N-carbamylglutamate (Carbaglu®) will enhance the ability of the liver to dispose of toxic ammonia which accumulates in several metabolic diseases ...
Detailed Description
Hyperammonemia associated with several rare inherited disorders frequently causes mental retardation, developmental disabilities and death. The overall goal of this study is to investigate the short-t...
Eligibility Criteria
Inclusion
- Between 1 day - 70 years of age
- Viable neonates, neonates with uncertain viability are excluded Diagnosed with one of the following five inborn errors of metabolism: NAGS, CPSI,PA, MMA, or OTC deficiency.
- Diagnostic requirements:
- NAGS deficiency - Identification of pathogenic mutation and/or decreased (\<20% of control) NAGS enzyme activity in liver
- CPSI deficiency - decreased (\<20% of control) CPSI enzyme activity in liver deficiency of liver CPSI in the presence of normal or substantial activity of OTC (Tuchman et al 1980) and/or molecular confirmation of deleterious mutations (Summary et al 2003).
- High level of clinical suspicion of NAGS or CPSI deficiency - Failure to meet diagnostic criteria for either NAGS or CPSI deficiency as listed above, but:
- Recurrent hyperammonemic episodes (NH3 \>70umol/l) with elevated plasma glutamine (\>/= 800umol/l)
- Urinary orotate levels within normal limits (\</= 5 umol/mmol urine creatinine)
- Absence of argininosuccinic acid in blood or urine
- Low or normal level of citrulline (\</=92umol/l) and arginine (\</= 179 umol/l) and ornithine (\</=159umol/l) within normal limits in blood
- OTC deficiency- Identification of pathogenic mutation and/or-pedigree analysis consistent with familial hyperammonemia segregating in an x-linked semi-dominant pattern and/or -\<20% of control OTC activity in liver and/or -elevated urinary orotate (\>20%umol/mmol creatinine) after allopurinol challenge test
- PA and MMA- diagnostic urine organic acid analysis and confirmation of absence of responsiveness to biotin and vitamin B12 respectively.
Exclusion
- Subjects acutely ill on day of the study
- Pregnant females- documentation of a negative pregnancy test within a week prior to testing is required for females 12 years and older, unless having a menstrual period during that week or other circumstances which preclude pregnancy (e.g. hysterectomy, menopause)
- Subjects with hyperammonemia caused by other urea cycle disorders, lysinuric protein intolerance, mitochondrial disorders, congenital lactic academia, fatty acid oxidation defects and primary liver disease
- Subjects requiring a peripherally inserted central catheter (PICC) for blood draws may need to be moderately sedated and are excluded
- Subjects with hemoglobin \< 9 g/dl
Key Trial Info
Start Date :
August 1 2008
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
June 30 2020
Estimated Enrollment :
52 Patients enrolled
Trial Details
Trial ID
NCT00843921
Start Date
August 1 2008
End Date
June 30 2020
Last Update
February 17 2020
Active Locations (1)
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1
Childrens Research Institute
Washington D.C., District of Columbia, United States, 20010