Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate
Primary Purpose
Urea Cycle Disorders, Inborn, Inborn Errors of Metabolism, Propionic Acidemia
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
N-carbamylglutamate
Sponsored by
About this trial
This is an interventional treatment trial for Urea Cycle Disorders, Inborn focused on measuring Ureagenesis, Urea cycle, Inborn errors of metabolism
Eligibility 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 Institutional Review Board (IRB) Policies and Procedures.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
N-carbamylglutamate (Carbaglu)
Arm Description
Outcomes
Primary Outcome Measures
Rate of ureagenesis
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01341379
First Posted
April 22, 2011
Last Updated
May 28, 2014
Sponsor
Children's Hospital of Philadelphia
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1. Study Identification
Unique Protocol Identification Number
NCT01341379
Brief Title
Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate
Official Title
Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate
Study Type
Interventional
2. Study Status
Record Verification Date
May 2014
Overall Recruitment Status
Withdrawn
Why Stopped
Lack of funding
Study Start Date
December 2010 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Children's Hospital of Philadelphia
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urea Cycle Disorders, Inborn, Inborn Errors of Metabolism, Propionic Acidemia, Methylmalonic Acidemia, Carbamyl Phosphate Synthetase Deficiency
Keywords
Ureagenesis, Urea cycle, Inborn errors of metabolism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
N-carbamylglutamate (Carbaglu)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
N-carbamylglutamate
Other Intervention Name(s)
Carbaglu
Intervention Description
N-carbamylglutamate: 200 mg/kg/day for 3 days, divided into 4 daily oral doses
Primary Outcome Measure Information:
Title
Rate of ureagenesis
Description
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.
Time Frame
3 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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 Institutional Review Board (IRB) Policies and Procedures.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Yudkoff, MD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
20566609
Citation
Ah Mew N, McCarter R, Daikhin Y, Nissim I, Yudkoff M, Tuchman M. N-carbamylglutamate augments ureagenesis and reduces ammonia and glutamine in propionic acidemia. Pediatrics. 2010 Jul;126(1):e208-14. doi: 10.1542/peds.2010-0008. Epub 2010 Jun 21.
Results Reference
result
PubMed Identifier
20338795
Citation
Yudkoff M, Ah Mew N, Daikhin Y, Horyn O, Nissim I, Nissim I, Payan I, Tuchman M. Measuring in vivo ureagenesis with stable isotopes. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S37-41. doi: 10.1016/j.ymgme.2010.02.017. Epub 2010 Feb 26.
Results Reference
result
PubMed Identifier
19660971
Citation
Ah Mew N, Payan I, Daikhin Y, Nissim I, Nissim I, Tuchman M, Yudkoff M. Effects of a single dose of N-carbamylglutamate on the rate of ureagenesis. Mol Genet Metab. 2009 Dec;98(4):325-30. doi: 10.1016/j.ymgme.2009.07.010. Epub 2009 Jul 14. Erratum In: Mol Genet Metab. 2010 Apr;99(4):440.
Results Reference
result
PubMed Identifier
18414145
Citation
Tuchman M, Caldovic L, Daikhin Y, Horyn O, Nissim I, Nissim I, Korson M, Burton B, Yudkoff M. N-carbamylglutamate markedly enhances ureagenesis in N-acetylglutamate deficiency and propionic acidemia as measured by isotopic incorporation and blood biomarkers. Pediatr Res. 2008 Aug;64(2):213-7. doi: 10.1203/PDR.0b013e318179454b.
Results Reference
result
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Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate
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