Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate
This study is currently recruiting participants.
Verified October 2012 by Children's Hospital of Philadelphia
Sponsor:
Children's Hospital of Philadelphia
Collaborator:
Information provided by (Responsible Party):
Marc Yudkoff, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01341379
First received: April 22, 2011
Last updated: October 26, 2012
Last verified: October 2012
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Purpose
Hyperammonemia, which can cause brain damage, occurs in many different kinds of inborn errors of metabolism. The investigators propose to determine if short-term (3 day) treatment with N-carbamylglutamate can diminish hyperammonemia by enhancing ureagenesis in these patients. The investigators propose here a short-term (3 day) trial. If it succeeds, the investigators would consider more extensive long-term studies of the drug.
| Condition | Intervention | Phase |
|---|---|---|
|
Urea Cycle Disorders, Inborn Inborn Errors of Metabolism Propionic Acidemia Methylmalonic Acidemia Carbamyl Phosphate Synthetase Deficiency |
Drug: N-carbamylglutamate |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate |
Resource links provided by NLM:
Genetics Home Reference related topics:
argininosuccinic aciduria
ataxia neuropathy spectrum
carbamoyl phosphate synthetase I deficiency
childhood myocerebrohepatopathy spectrum
citrullinemia
deoxyguanosine kinase deficiency
methylmalonic acidemia
mitochondrial neurogastrointestinal encephalopathy disease
myoclonic epilepsy myopathy sensory ataxia
N-acetylglutamate synthase deficiency
ornithine translocase deficiency
propionic acidemia
succinic semialdehyde dehydrogenase deficiency
Drug Information available for:
Carglumic acid
U.S. FDA Resources
Further study details as provided by Children's Hospital of Philadelphia:
Primary Outcome Measures:
- Rate of ureagenesis [ Time Frame: 3 days ] [ Designated as safety issue: No ]Goal is to determine whether a 3 day trial of N-carbamylglutamate increases ureagenesis in patients with urea cycle defects and other inborn errors of metabolism.
| Estimated Enrollment: | 80 |
| Study Start Date: | December 2010 |
| Estimated Study Completion Date: | June 2016 |
| Estimated Primary Completion Date: | June 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: N-carbamylglutamate (Carbaglu) |
Drug: N-carbamylglutamate
N-carbamylglutamate: 200 mg/kg/day for 3 days, divided into 4 daily oral doses
Other Name: Carbaglu
|
Detailed Description:
- To determine whether brief (3 day) treatment with N-carbamylglutamate can improve ureagenesis in adult healthy controls and patients with the following inborn errors of metabolism: N-acetylglutamate synthetase deficiency, propionic acidemia, methylmalonic acidemia, carbamylphosphate synthase deficiency, ornithine transcarbamylase deficiency and the syndrome of hyperammonemia, hypoglycemia and hyperinsulinemia (HHH Syndrome).
- To determine if such treatment improves other indicators of abnormal nitrogen metabolism such as elevated blood levels of glutamine, glycine and alanine.
Eligibility| Ages Eligible for Study: | 3 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Criteria
Inclusion Criteria:
- Age range: males or females, ages 3 years - 70 years
- Condition(s): N-acetylglutamate synthetase deficiency, propionic acidemia, methylmalonic acidemia, carbamylphosphate synthase deficiency, ornithine transcarbamylase deficiency and the syndrome of hyperammonemia, hypoglycemia and hyperinsulinemia.
- In addition, healthy volunteers will be studied (ages 18 years - 50 years).
Exclusion Criteria:
- Acutely ill on day of study (fever, evidence of hyperammonemia - ataxia, worsening obtundation, focal neurologic signs, seizures, increased intracranial pressure, vomiting, signs of acute respiratory or enteric illness, headache, confusion, disorientation, acute personality change).
- Girls 11 years of age must have a negative urine/serum pregnancy test within 1 week prior to testing unless having a menstrual period during week of test
- Lactating females
- Hyperammonemia probably refractory to N-carbamylglutamate: other urea cycle disorders (UCD), lysinuric protein intolerance, mitochondrial disorders, congenital lactic acidemia, fatty acid oxidation defects or primary liver disease.
- Amount of blood necessary for study exceeds safe limits.
- Any investigational drug use within 30 days prior to enrollment.
- Parents/guardians or subjects who, in the opinion of the PI, may be non-compliant with study schedules or procedures.
- Subjects who do not meet all the enrollment criteria may not be enrolled. Any violations of these criteria will be reported in accordance with IRB Policies and Procedures.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01341379
Contacts
| Contact: Marc Yudkoff, MD | 215-590-7474 | yudkoff@email.chop.edu |
| Contact: Irma Payan, CRNP | 215-590-6236 | payan@email.chop.edu |
Locations
| United States, Pennsylvania | |
| Children's Hospital of Philadelphia | Recruiting |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Contact: Marc Yudkoff, MD 215-590-7474 yudkoff@email.chop.edu | |
| Contact: Irma Payan, CRNP 215-590-6236 payan@email.chop.edu | |
| Principal Investigator: Marc Yudkoff, MD | |
Sponsors and Collaborators
Children's Hospital of Philadelphia
Investigators
| Principal Investigator: | Marc Yudkoff, MD | Children's Hospital of Philadelphia |
More Information
Additional Information:
Publications:
| Responsible Party: | Marc Yudkoff, Division Chief, Children's Hospital of Philadelphia |
| ClinicalTrials.gov Identifier: | NCT01341379 History of Changes |
| Other Study ID Numbers: | 10-007806, R01HD058567 |
| Study First Received: | April 22, 2011 |
| Last Updated: | October 26, 2012 |
| Health Authority: | United States: Food and Drug Administration United States: Federal Government |
Keywords provided by Children's Hospital of Philadelphia:
|
Ureagenesis Urea cycle Inborn errors of metabolism |
Additional relevant MeSH terms:
|
Metabolism, Inborn Errors Urea Cycle Disorders, Inborn Propionic Acidemia Amino Acid Metabolism, Inborn Errors Carbamoyl-Phosphate Synthase I Deficiency Disease Genetic Diseases, Inborn Metabolic Diseases |
Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Mitochondrial Diseases |
ClinicalTrials.gov processed this record on June 17, 2013