Status unknownNCT00843921Updated Feb 17, 2020

N-Carbamylglutamate (Carbaglu) In The Treatment Of Hyperammonemia

A Phase 2/3 interventional study of N-carbamylglutamate in Inborn Errors of Metabolism, sponsored by Mendel Tuchman. Status unknown at 1 site in United States. Open to participants aged 1 Day to 70 Years. Per ClinicalTrials.gov, last updated 2020-02-17.

Sponsored by Mendel Tuchman · Phase 2/3, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Feb 2020), so the status shown — last known as Active, not recruiting — may be out of date.

Phase: Phase 2/3
Study type: Interventional
Enrollment: 52
Allocation: Not applicable
Ages: 1 Day to 70 Years
Sex: All

Study summary

This study is based on the hypothesis that a new drug N-carbamylglutamate (Carbaglu®) will enhance the ability of the liver to dispose of toxic ammonia which accumulates in several metabolic diseases including urea cycle disorders and organic acid disorders.

Read the detailed description

Hyperammonemia associated with several rare inherited disorders frequently causes mental retardation, developmental disabilities and death. The overall goal of this study is to investigate the short-term efficacy and safety of the orphan drug, N-Carbamyl-L-glutamate (Carbaglu®, abbreviated as NCG), for the treatment of hyperammonemia in rare inherited disorders: carbamyl phosphate synthetase I (CPSI) deficiency, NAGS deficiency, ornithine transcarbamylase (OTC) deficiency, propionic acidemia (PA) and methylmalonic acidemia (MMA).

The primary aims are:

To investigate whether 3-day treatment with NCG can improve or restore ureagenesis capacity in patients with NAGS, CPSI or OTC deficiency using as surrogate markers: [13C] label incorporation into urea and plasma levels of ammonia, urea and glutamine. In addition, to determine whether treatment with NCG in OTC deficiency increases the production of a nitrogen containing intermediate, orotic acid, as a mechanism for eliminating nitrogen in lieu of urea.
To investigate whether ureagenesis capacity is deficient in patients with PA and MMA and whether 3-day treatment with NCG can improve or restore ureagenesis capacity in all or some of these patients.
To evaluate the safety of short-term (3-day) treatment with NCG in the above patients using clinical and laboratory parameters.

The hypothesis is that ureagenesis capacity as evidenced by [13C] incorporation into urea is deficient in each of these five disorders and that treatment with NCG will improve or restore ureagenesis in patients affected by them. The study will be conducted in the General Clinical Research Centers (GCRC) of the Children's National Medical Center, Washington, D.C. and the Children's Hospital of Philadelphia. Patients (1 day to 70 years of age) with any of the five disorders are eligible for the study. They will all be tested in a short-term trial using surrogate markers (incorporation of [13C] label from Na-acetate into urea, and plasma levels of ammonia, urea and glutamine) before and immediately following 3 days of treatment with NCG. The patients will also be evaluated for short-term safety of NCG using clinical and laboratory parameters. The results of this study will provide important efficacy data, which should help to bring Carbaglu®) to the US market for the benefit of patients with any of these orphan diseases found to be responsive to NCG in this trial.

Conditions studied

Inborn Errors of Metabolism

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Keywords

Hyperammonemia

In context

Metabolism, Inborn Errors

152 studies on the registry are indexed under Metabolism, Inborn Errors; 22 are open to participants now.

This study's enrollment of 52 is above the median of 26 across 89 interventional studies indexed under Metabolism, Inborn Errors.

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Lead sponsor

Mendel Tuchman is the lead sponsor of 3 studies on the registry; none are open to participants now.

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

Who can participate

Ages eligible: 1 Day to 70 Years
Sexes eligible: All
Accepts healthy volunteers: No

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Inclusion criteria

Between 1 day - 70 years of age
Viable neonates, neonates with uncertain viability are excluded Diagnosed with one of the following five inborn errors of metabolism: NAGS, CPSI,PA, MMA, or OTC deficiency.
Diagnostic requirements:
- NAGS deficiency - Identification of pathogenic mutation and/or decreased (\<20% of control) NAGS enzyme activity in liver
- CPSI deficiency - decreased (\<20% of control) CPSI enzyme activity in liver deficiency of liver CPSI in the presence of normal or substantial activity of OTC (Tuchman et al 1980) and/or molecular confirmation of deleterious mutations (Summary et al 2003).
- High level of clinical suspicion of NAGS or CPSI deficiency - Failure to meet diagnostic criteria for either NAGS or CPSI deficiency as listed above, but:
  1. Recurrent hyperammonemic episodes (NH3 >70umol/l) with elevated plasma glutamine (>/= 800umol/l)
  2. Urinary orotate levels within normal limits (\</= 5 umol/mmol urine creatinine)
  3. Absence of argininosuccinic acid in blood or urine
  4. Low or normal level of citrulline (\</=92umol/l) and arginine (\</= 179 umol/l) and ornithine (\</=159umol/l) within normal limits in blood
- OTC deficiency- Identification of pathogenic mutation and/or-pedigree analysis consistent with familial hyperammonemia segregating in an x-linked semi-dominant pattern and/or -\<20% of control OTC activity in liver and/or -elevated urinary orotate (>20%umol/mmol creatinine) after allopurinol challenge test
- PA and MMA- diagnostic urine organic acid analysis and confirmation of absence of responsiveness to biotin and vitamin B12 respectively.

Exclusion criteria

Exclusion Criteria:

Subjects acutely ill on day of the study
Pregnant females- documentation of a negative pregnancy test within a week prior to testing is required for females 12 years and older, unless having a menstrual period during that week or other circumstances which preclude pregnancy (e.g. hysterectomy, menopause)
Subjects with hyperammonemia caused by other urea cycle disorders, lysinuric protein intolerance, mitochondrial disorders, congenital lactic academia, fatty acid oxidation defects and primary liver disease
Subjects requiring a peripherally inserted central catheter (PICC) for blood draws may need to be moderately sedated and are excluded
Subjects with \< 9 g/dl

Terms in these criteria, in plain language(1)

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.

Hemoglobin (Hb): The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Study design

Phase: Phase 2 / Phase 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 52 participants (actual)

Study arms

Experimental
Carbaglu
Investigate whether a 3-day treatment with NCG can improve or restore urea genesis capacity in patients with NAGS, CPSI, or OTC deficiency or PA or MMA using surrogate markers: \[13C\] label incorporation into urea and plasma levels of ammonia, urea nitrogen (BUN) and amino acids
Drug: N-carbamylglutamate

Interventions

DrugN-carbamylglutamate
100 mg/kg/day or 2.2 g/M2/day in 3-4 divided doses for 3 days
Also known as: Carglumic acid, Carbaglu

What researchers measure

Primary outcomes

Rate of ureagenesis as determined by 13C enrichment of urea
Time frame: 3 days of treatment

Secondary outcomes

Plasma ammonia concentration
Time frame: 3 days
Plasma amino acid levels
Time frame: 3 days
Urine Orotic Acid
Only in patients with OTC deficiency
Time frame: 3 days
Blood Urea Nitrogen (BUN)
Time frame: 3 days
Routine safety laboratory tests (CBC, LFTs, Creatinine)
Time frame: 3 days

Study locations

1 site

Childrens Research Institute
Washington, District of Columbia 20010, United States

References and documents

Individual participant data

Plan to share: Yes — Individual participant data will be shared with that particular participant

No publications or documents are linked to this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 17, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00843921
Lead sponsor: Mendel Tuchman
Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Responsible party: Mendel Tuchman (MD, Children's National Research Institute) — Sponsor-investigator
First posted: Feb 13, 2009
Start date: Aug 2008
Primary completion: Apr 25, 2018
Completion: Jun 30, 2020 (estimated)
Last update: Feb 17, 2020

Study contacts

Mendel Tuchman, MD

principal investigator · Children's National Research Institute

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is status unknown, as verified in Feb 2020. You cannot join it, but the record below documents what was studied.

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Discussion

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Studies of the drug tested here: Carglumic acid

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