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Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01341379
Recruitment Status : Withdrawn (Lack of funding)
First Posted : April 25, 2011
Last Update Posted : May 29, 2014
Sponsor:
Collaborator:
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Urea Cycle Disorders, Inborn Inborn Errors of Metabolism Propionic Acidemia Methylmalonic Acidemia Carbamyl Phosphate Synthetase Deficiency Drug: N-carbamylglutamate Phase 2

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate
Study Start Date : December 2010
Primary Completion Date : August 2012
Study Completion Date : August 2012


Arms and Interventions

Arm Intervention/treatment
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


Outcome Measures

Primary Outcome Measures :
  1. Rate of ureagenesis [ Time Frame: 3 days ]
    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.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 70 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
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 Institutional Review Board (IRB) Policies and Procedures.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01341379


Sponsors and Collaborators
Children's Hospital of Philadelphia
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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 ( U.S. NIH Grant/Contract )
First Posted: April 25, 2011    Key Record Dates
Last Update Posted: May 29, 2014
Last Verified: May 2014

Keywords provided by Marc Yudkoff, Children's Hospital of Philadelphia:
Ureagenesis
Urea cycle
Inborn errors of metabolism

Additional relevant MeSH terms:
Amino Acid Metabolism, Inborn Errors
Urea Cycle Disorders, Inborn
Metabolism, Inborn Errors
Acidosis
Propionic Acidemia
Carbamoyl-Phosphate Synthase I Deficiency Disease
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Metabolic Diseases
Acid-Base Imbalance
Mitochondrial Diseases