search
Back to results

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Withdrawn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
Children's Hospital of Philadelphia
About
Eligibility
Locations
Arms
Outcomes
Full info

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

3 Years - 70 Years (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

    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)
    search

    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

    Learn more about this trial

    Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate

    We'll reach out to this number within 24 hrs