Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate

Brief Title

Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate

Official Title

Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Rate of ureagenesis


Condition

Urea Cycle Disorders, Inborn

Intervention

N-carbamylglutamate

Study Arms / Comparison Groups

 N-carbamylglutamate (Carbaglu)
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

0

Start Date

December 2010

Completion Date

August 2012

Primary Completion Date

August 2012

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.
      

Gender

All

Ages

3 Years - 70 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Marc Yudkoff, MD, , 



Administrative Informations


NCT ID

NCT01341379

Organization ID

10-007806

Secondary IDs

R01HD058567

Responsible Party

Principal Investigator

Study Sponsor

Children's Hospital of Philadelphia

Collaborators

 Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Study Sponsor

Marc Yudkoff, MD, Principal Investigator, Children's Hospital of Philadelphia


Verification Date

May 2014