Short-Term Outcome of N-Carbamylglutamate in the Treatment of Acute

Status Completed

Clinical Trial Summary

The overall objective of this drug trial is to determine whether the treatment of acute hyperammonemia with N-carbamyl-L-glutamate (NCG, Carglumic acid) 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 episode of hyperammonemia.

Clinical Trial Description

This is a double-blind, placebo-controlled, 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 the entry to the study. Safety tests consisting of complete blood count (CBC), liver and kidney function tests, and coagulation profile (PTT/INR) will be performed before treatment, between days 3-5 of treatment, and just prior to discontinuation of NCG. An electrocardiogram will be performed before treatment and on the third day of treatment or before discharge if earlier. ;

Study Design

Related Conditions & MeSH terms

Acidosis
Carbamoyl-Phosphate Synthase I Deficiency Disease
Deficiency Diseases
Hyperammonemia
Methylmalonic Acidemia
Ornithine Carbamoyltransferase Deficiency
Propionic Acidemia
Propionic Acidemia, Type I and/or Type II

Clinical Trial Details

NCT number	NCT01599286
Study type	Interventional
Source	Children's National Research Institute
Contact
Status	Completed
Phase	Phase 2
Start date	September 1, 2012
Completion date	April 30, 2020

View Details

See also
Status	Clinical Trial	Phase
Enrolling by invitation	`NCT05842837` - A Non-Interventional Post-Authorization Study of Carbaglu for the Treatment of Hyperammonemia Due to MMA and PA
Completed	`NCT02426775` - Carglumic Acid in Methylmalonic Acidemia and Propionic Acidemia	Phase 3
Terminated	`NCT04581785` - Gene Therapy With hLB-001 in Pediatric Patients With Severe Methylmalonic Acidemia	Phase 1/Phase 2
Recruiting	`NCT05295433` - An Extension Study to Evaluate the Long-Term Safety and Clinical Activity of mRNA-3705 in Participants Previously Enrolled in Other Clinical Studies of mRNA-3705	Phase 1/Phase 2
Terminated	`NCT04836494` - A First in Human, Dose Escalation Study to Evaluate the Safety and Tolerability of BBP-671 in Healthy Volunteers and Patients With Propionic Acidemia or Methylmalonic Acidemia	Phase 1
Completed	`NCT03484767` - "The MaP Study": Mapping the Patient Journey in MMA and PA
Terminated	`NCT04732429` - Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia	Phase 2
Recruiting	`NCT00078078` - Clinical and Laboratory Study of Methylmalonic Acidemia
Recruiting	`NCT05040178` - An Observational Study of Carbaglu® for the Treatment of MMA and PA in Adults and Pediatrics
Active, not recruiting	`NCT05506254` - Long-term Follow-up Study of Patients Who Received hLB-001 Gene Therapy
Recruiting	`NCT04176523` - Understanding the Long-Term Management of Organic Acidemia Patients With CARBAGLU®: A Mixed Methods Approach
Recruiting	`NCT01289158` - Combined Malonic and Methylmalonic Aciduria (CMAMMA): Gene Identification and Outcome Study	N/A
Withdrawn	`NCT01341379` - Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate	Phase 2
Recruiting	`NCT04899310` - A Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of mRNA-3705 in Participants With Isolated Methylmalonic Acidemia	Phase 1/Phase 2
Terminated	`NCT05438485` - Natural History Study of Patients With Methylmalonic Acidemia and Propionic Acidemia

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

Short-Term Outcome of N-Carbamylglutamate in the Treatment of Acute Hyperammonemia — STO

Clinical Trial Summary

Clinical Trial Description

Study Design

Related Conditions & MeSH terms