Clinical Trial: N-Carbamylglutamate (Carbaglu) In The Treatment Of Hyperammonemia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: N-Carbamylglutamate (Carbaglu) In The Treatment Of Hyperammonemia

Brief 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.

Detailed Summary:

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:

  1. 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.
  2. 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.
  3. 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,
Sponsor: Mendel Tuchman

Current Primary Outcome: Rate of ureagenesis as determined by 13C enrichment of urea [ Time Frame: 3 days of treatment ]

Original Primary Outcome: Rate of ureagenesis as determined by isotopic enrichment and plasma ammonia, urea and amino acid levels. Routine safety blood laboratory tests [ Time Frame: 3 days of treatment ]

Current Secondary Outcome:

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


Original Secondary Outcome:

Information By: Children's Research Institute

Dates:
Date Received: February 12, 2009
Date Started: August 2008
Date Completion: July 2018
Last Updated: August 15, 2016
Last Verified: August 2016