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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Last refreshed on: 12 December 2020
Main ID:  NCT01599286
Date of registration: 11/05/2012
Prospective Registration: Yes
Primary sponsor: Mendel Tuchman
Public title: Short-Term Outcome of N-Carbamylglutamate in the Treatment of Acute Hyperammonemia
Scientific title: Short-Term Outcome of N-Carbamylglutamate in the Treatment of Acute Hyperammonemia
Date of first enrolment: September 2012
Target sample size: 114
Recruitment status: Active, not recruiting
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).  
Phase:  Phase 2
Countries of recruitment
United States
Name:     Mendel Tuchman, MD
Affiliation:  Children's National Research Institute
Key inclusion & exclusion criteria

Inclusion Criteria

o Aged older than 1 week with an established diagnosis of CPSD or OTCD (as follows):

- Diagnosed with late-onset CPSD confirmed by detection of pathogenic mutation(s),
and/or decreased (<20% of control) CPS enzyme activity in liver OR

- Diagnosed with late-onset OTCD by detection of pathogenic OTC mutation, OR decreased
(<20% of control) OTC enzyme activity in liver OR elevated urinary orotate (greater
than 20 ┬ÁM/mM) following allopurinol loading with absence of argininosuccinic acid

AND: Subject or subject's first-degree relative had plasma ammonia level =100 mcmol/L >1
week of age


o An established diagnosis of PA or MMA (as follows):

- Diagnosed with PA by semi-quantitative urine organic acid analysis, defined as presence
of elevated Methylcitric acid and normal methylmalonic acid levels and no evidence of
biotin related disorders in the organic acid analysis


- Diagnosed with MMA by semi-quantitative urine organic acid analysis, defined as elevation
of methylmalonic acid and no evidence of vitamin B12 dependent disorder on plasma amino
acid analysis (B12 dependency is defined by documented B12 responsiveness)

AND: Subject or subject's first-degree relative had plasma ammonia level at any time =100

- Able to receive medications orally, by nasogastric (NG)-tube or by gastric (G)-tube

- No concomitant illness which would preclude safe participation as judged by the

- If post-menarcheal must have a negative pregnancy test prior to administration of
study drug at each episode

- Signed informed consent by the subject or the subject's legally acceptable

Exclusion Criteria

- Administration of NCG within 7 days of participation in the study

- Use of any other investigational drug, biologic, or therapy

- Planned participation in any other clinical trial

- Diagnosis of any medical condition causing hyperammonemia which is not PA/MMA, CPSD or
OTCD. Other urea cycle disorders will be excluded from this study

- Any clinical or laboratory abnormality or medical condition that, at the discretion of
the investigator, may put the subject at an additional risk by participating in this

- Has had a liver transplant

- Is not expected to be compliant with this study in terms of returning to site for
subsequent episodes of hyperammonemia crises

- Is pregnant

Age minimum: N/A
Age maximum: 99 Years
Gender: All
Health Condition(s) or Problem(s) studied
Carbamoyl-Phosphate Synthase I Deficiency Disease
Methylmalonic Acidemia
Ornithine Carbamoyltransferase Deficiency
Propionic Acidemia, Type I and/or Type II
Drug: Carbaglu
Drug: Placebo
Drug: Standard of Care Treatment
Primary Outcome(s)
Trajectory of Change in Ammonia During Hospitalization for Hyperammonemia [Time Frame: Admission, Post Dialysis, 12, 24, 36, 48 hours and daily for 7 days or until discharge]
Secondary Outcome(s)
Safety of NCG [Time Frame: Admission, 12, 24, 36, 48 hours and daily until day 7 after episode (or discharge, whichever is sooner)]
Secondary ID(s)
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Boston Children's Hospital
Children's Hospital Colorado
Children's Hospital of Philadelphia
Children's National Research Institute
Icahn School of Medicine at Mount Sinai
Stanford University
University Hospitals Cleveland Medical Center
University of California, Los Angeles
University of Pittsburgh
Ethics review
Results available:
Date Posted:
Date Completed:
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