Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate

This study is currently recruiting participants.
Verified July 2013 by Children's Hospital of Philadelphia
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Marc Yudkoff, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01341379
First received: April 22, 2011
Last updated: July 30, 2013
Last verified: July 2013
  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:


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: July 30, 2013
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 April 17, 2014