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

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

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

Brief Summary:

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.


Detailed Summary:

This is a double-blind randomized clinical drug trial to evaluate the efficacy of NCG in the treatment of two organic acidemias (severe PA and MMA), and two urea-cycle disorders (late-onset CPSD and OTCD).

Primarily, the investigators want to determine whether NCG treatment of acute hyperammonemia in severe, neonatal-onset PA, MMA,CPSD and OTCD is efficacious, and whether it is safe. The investigators will approach this task in two ways:

  1. Assess whether NCG treatment is effective

    The objective of this study is to assess whether NCG is efficacious in treating hyperammonemia and improving outcome:

    - The investigators will realize this goal by randomizing each hyperammonemic episode from every subject to NCG (NCG)+standard treatment (NCG-STD) versus placebo+standard treatment (PLBO-STD) and subsequently gauging response with the primary outcome of plasma ammonia levels, in addition to the plasma glutamine, the Functional Status Scale, and the length of hospitalization.

  2. Safety

The primary safety outcome of the study will be the assessed via the rate of Serious Adverse Events (SAEs) defined in this study as death or substantial prolongation of hospitalization, as patients are hospitalized as part of entry to the study.

Safety tests consisting of complete blood count (CBC), liver and kidney function tests, coagulation profile (PTT/INR) will be performed before treatment, on the third day of treatment, and just prior to discontinuation of NCG. An electrocardiogram will be performed before treatment and on the t
Sponsor: Mendel Tuchman

Current Primary Outcome: Trajectory of change in ammonia during hospitalizations for hyperammonemia [ Time Frame: Admission, Post Dialysis, 12, 24, 36, 48 hours and daily for 7 days or until discharge. ]

Change in ammonia and functional status.


Original Primary Outcome: Same as current

Current Secondary Outcome: Safety of NCG [ Time Frame: Admission, 12, 24, 36, 48 hours and daily until day 7 after episode (or discharge, whichever is sooner) ]

The primary safety outcome of the study will be the assessed via the rate of Serious Adverse Events (SAEs) defined in this study as death or substantial prolongation of hospitalization, as patients are hospitalized as part of entry to the study.

Safety tests consisting of complete blood count (CBC), liver and kidney function tests, coagulation profile (PTT/INR) will be performed before treatment, on the third day of treatment, and just prior to discontinuation of NCG. A electrocardiogram test will be given before treatment and repeated on the third day of treatment (48 hours following the initial drug administration) or before discharge if earlier, to check for cardiac toxicity.



Original Secondary Outcome: Safety of NCG [ Time Frame: Admission, 12, 24, 36, 48 hours and daily until day 7 after episode (or discharge, whichever is sooner) ]

The primary safety outcome of the study will be the assessed via the rate of Serious Adverse Events (SAEs) defined in this study as death or substantial prolongation of hospitalization, as patients are hospitalized as part of entry to the study.

Safety tests consisting of complete blood count (CBC), liver and kidney function tests, coagulation profile (PTT/INR) will be performed before treatment, on the third day of treatment, and just prior to discontinuation of NCG.



Information By: Children's Research Institute

Dates:
Date Received: May 11, 2012
Date Started: September 2012
Date Completion: December 2019
Last Updated: April 4, 2017
Last Verified: April 2017