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WithdrawnNCT01341379Updated May 29, 2014

Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate

A Phase 2 interventional study of N-carbamylglutamate in Urea Cycle Disorders, Inborn, Inborn Errors of Metabolism and Propionic Acidemia, sponsored by Children's Hospital of Philadelphia. Withdrawn. Open to participants aged 3 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2014-05-29.

Sponsored by Children's Hospital of Philadelphia · Phase 2, Interventional, and Treatment

Why this study was withdrawn
Lack of funding
Phase
Phase 2
Study type
Interventional
Enrollment
0
Allocation
Not applicable
Ages
3 Years to 70 Years
Sex
All
01

Study 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.

Read the 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.
02

Conditions studied

  • Urea Cycle Disorders, Inborn
  • Inborn Errors of Metabolism
  • Propionic Acidemia
  • Methylmalonic Acidemia
  • Carbamyl Phosphate Synthetase Deficiency

Keywords

  • Ureagenesis
  • Urea cycle
  • Inborn errors of metabolism
03

In context

Urea Cycle Disorders, Inborn

66 studies on the registry are indexed under Urea Cycle Disorders, Inborn; 14 are open to participants now.

Browse Urea Cycle Disorders, Inborn studies →

Lead sponsor

Children's Hospital of Philadelphia is the lead sponsor of 489 studies on the registry; 90 are open to participants now.

Of its 28 completed or terminated interventional studies of FDA-regulated products, 22 (79%) have results posted.

Browse Children's Hospital of Philadelphia studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
3 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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 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 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.
Terms in these criteria, in plain language(2)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Relapsed and refractory

Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
0 participants (actual)

Study arms

  • Experimental
    N-carbamylglutamate (Carbaglu)

    Drug: N-carbamylglutamate

Interventions

  • DrugN-carbamylglutamate

    N-carbamylglutamate: 200 mg/kg/day for 3 days, divided into 4 daily oral doses

    Also known as: Carbaglu

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 3 days

07

Study locations

No study locations are listed for this record.

08

References and documents

Publications

  • 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. PubMed 20566609 ↗
  • 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. PubMed 20338795 ↗
  • 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. PubMed 19660971 ↗
  • 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. PubMed 18414145 ↗
09

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Dec 2010, a primary completion of Aug 2012 and a completion of Aug 2012. It does not say whether these dates are actual or estimated.

How these figures are worked out, and which studies are left out of them.

Registered
Apr 22, 2011
First posted
Apr 25, 2011
Start
Dec 2010
Primary completionActual
Aug 2012
CompletionActual
Aug 2012
Last update
May 29, 2014
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on May 29, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01341379
Lead sponsor
Children's Hospital of Philadelphia
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Responsible party
Marc Yudkoff (Division Chief, Children's Hospital of Philadelphia) — Principal investigator
First posted
Apr 25, 2011
Start date
Dec 2010
Primary completion
Aug 2012
Completion
Aug 2012
Last update
May 29, 2014

Study contacts

Marc Yudkoff, MD
principal investigator · Children's Hospital of Philadelphia

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is withdrawn, as verified in May 2014. You cannot join it, but the record below documents what was studied.

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