Short-term Outcome of N-Carbamylglutamate in the Treatment of Acute Hyperammonemia

Description

The overall objective of this drug trial is to determine whether treatment of acute hyperammonemia with N-carbamyl-L-glutamate (NCG, Carglumic acid, NCG) in propionic acidemia (PA), methylmalonic acidemia (MMA), late-onset CPS1 deficiency (CPSD) and late-onset Ornithine transcarbamylase deficiency (OTCD) accelerates the resolution of hyperammonemia efficiently and safely. The primary goal is to determine if the study drug (NCG) efficiently reduces ammonia levels following a hyperammonemia episode(s). Secondly, the investigators want to know if treatment with this study drug (NCG) efficiently improves neurologic function, reduces plasma glutamine levels and lessens the duration of hospitalization after each hyperammonemic episode.

Study Start Date

September 2012

Estimated Completion Date

March 2017

Interventions

  • Drug: Carbaglu
  • Drug: Standard Care Treatment
  • Drug: Placebo

Specialties

  • Pediatrics: Clinical Pharmacology,Neonatology
  • Pharmacy: Drug Trials

MeSH Terms

  • Amino Acid Metabolism
  • Carbamoyl-Phosphate Synthase I Deficiency Disease
  • Hyperammonemia
  • Ornithine Carbamoyltransferase Deficiency Disease
  • Propionic Acidemia

Study ID

Children's Research Institute -- NCGC0008

Status

Unknown

Trial ID

NCT01599286

Study Type

Interventional

Trial Phase

Phase 2

Enrollment Quota

144

Sponsor

Children's Research Institute

Inclusion Criteria

  • Aged 4 weeks to 18 years
  • Established diagnosis of PA, MMA, CPSD or OTCD as follows (one of the following):
  • Diagnosed with PA by 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 OR
  • Diagnosed with MMA by quantitative urine organic acid analysis, defined as elevation of methylmalonic acid and no evidence of vitamin B12 dependent disorder on plasma amino acid analysis OR
  • Diagnosed with late-onset CPSD by 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 absence of argininosuccinic acid
  • Subject or subject's first degree relative who:
  • Had plasma ammonia level at any time >200 µmol/l
  • If diagnosed PA/MMA (per above) had initial hyperammonemia ? 4 weeks of age
  • If diagnosed CPSD/OTCD (per above) had initial hyperammonemia > 4 weeks of age
  • 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
  • Signed informed consent by 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.
  • Diagnosis of any medical condition causing hyperammonemia which is not PA or MMA.
  • 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 study
  • Had a liver transplant

Gender

Both

Ages

18 Years and younger

Accepts Healthy Volunteers

No

Study Locations and Contact Information (14)

Study Location Distance Name Phone Email
Mount Sinai School of Medicine - New York, New York 46.8 miles Luca Fierro MS CGC 212-659-1477 luca.fierro@mssm.edu
Mount Sinai School of Medicine - New York, New York 46.8 miles None None None
The Childrens Hospital of Philadelphia CHOP - Philadelphia, Pennsylvania 134.5 miles None None None
Childrens Hospital Boston - Boston, Massachusetts 135.8 miles None None None
Childrens National Medical Center - Washington, District of Columbia 255.3 miles None None None
Childrens National Medical Center - Washington, District of Columbia 255.3 miles Sandra Yang MS CGC 202-476-5566 syang@childrensmational.org
University of Pittsburgh - Pittsburgh, Pennsylvania 354.7 miles None None None
University Hospitals of ClevelandRainbow Babies and Childrens Hospital - Cleveland, Ohio 434.6 miles None None None
The Childrens Hospital of Colorado - Aurora, Colorado 1,658.2 miles Curtis R Coughlin MS CGC 303-724-2310 Coughlin.Curtis@tchden.org
The Childrens Hospital of Colorado - Aurora, Colorado 1,658.2 miles None None None
University of California Los Angeles - Los Angeles, California 2,499.3 miles None None None
University of California Los Angeles - Los Angeles, California 2,499.3 miles Erica Chan MS 310-206-6581 ecchan@mednet.ucla.edu
Lucile Packard Childrens Hospital at Stanford - Palo Alto, California 2,600.0 miles Dina Chinichian 650-736-8166 dinacm@stanford.edu
Lucile Packard Childrens Hospital at Stanford - Palo Alto, California 2,600.0 miles None None None

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