Short-Term Outcome of N-Carbamylglutamate in the Treatment of Acute Hyperammonemia (STO)
Propionic Acidemia, Type I and/or Type II, Methylmalonic Acidemia, Carbamoyl-Phosphate Synthase I Deficiency Disease
About this trial
This is an interventional treatment trial for Propionic Acidemia, Type I and/or Type II focused on measuring Hyperammonemia, Propionic Acidemia (PA), Methylmalonic Acidemia (MMA), Late-Onset CPS1 Deficiency (CPSD), Late-Onset Ornithine Transcarbamylase Deficiency (OTCD), Carbaglu
Eligibility 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 µM/mM) following allopurinol loading with the absence of argininosuccinic acid
AND: Subject or subject's first-degree relative had plasma ammonia level ≥100 μmol/L >1 week of age
OR
o An established diagnosis of PA or MMA (as follows):
- Diagnosed with PA by semi-quantitative urine organic acid analysis, defined as the presence of elevated Methylcitric acid and normal methylmalonic acid levels and no evidence of biotin related disorders in the organic acid analysis
OR
- Diagnosed with MMA by semi-quantitative urine organic acid analysis, defined as an 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 μmol/L
- 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 investigator
- 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 representative
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 additional risk by participating in this study
- Has had a liver transplant
- Is not expected to be compliant with this study in terms of returning to the site for subsequent episodes of hyperammonemia crises
- Is pregnant
Sites / Locations
- University of California Los Angeles
- Lucile Packard Children's Hospital at Stanford
- The Children's Hospital of Colorado
- Children's National Medical Center
- Children's Hospital Boston
- Mount Sinai School of Medicine
- University Hospitals Cleveland Medical Center
- The Children's Hospital of Philadelphia (CHOP)
- University of Pittsburgh
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Active Comparator
Placebo Comparator
Parallel Trial Comparing NCG + Standard of Care Treatment
Placebo and Standard of Care Therapy