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Conducting an investigator-initiated randomized double-blinded intervention trial in acute decompensation of inborn errors of metabolism: Lessons from the N-Carbamylglutamate Consortium.

ABSTRACT: Organic acidemias and urea cycle disorders are ultra-rare inborn errors of metabolism characterized by episodic acute decompensation, often associated with hyperammonemia, resulting in brain edema and encephalopathy. Retrospective reports and translational studies suggest that N-carbamylglutamate (NCG) may be effective in reducing ammonia levels during acute decompensation in two organic acidemias, propionic and methylmalonic acidemia (PA and MMA), and in two urea cycle disorders, carbamylphosphate synthetase 1 and ornithine transcarbamylase deficiency (CPSD and OTCD). We established the 9-site N-carbamylglutamate Consortium (NCGC) in order to conduct two randomized double-blind, placebo-controlled trials of NCG in acute hyperammonemia of PA, MMA, CPSD and OTCD. Conducting clinical trials is challenging in any disease, but poses unique barriers and risks in the ultra-rare disorders. As the number of clinical trials in orphan diseases increases, evaluating the successes and opportunities for improvement in such trials is essential. We summarize herein the design, methods, experiences, challenges and lessons from the NCGC-conducted trials.

SUBMITTER: Ah Mew N

PROVIDER: S-EPMC6311376 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Conducting an investigator-initiated randomized double-blinded intervention trial in acute decompensation of inborn errors of metabolism: Lessons from the N-Carbamylglutamate Consortium.

Ah Mew Nicholas N Cnaan Avital A McCarter Robert R Choi Henry H Glass Penny P Rice Katie K Scavo Louis L Gillespie Catherine W CW Diaz George A GA Berry Gerard T GT Wong Derek D Konczal Laura L McCandless Shawn E SE Coughlin Ii Curtis R CR Weisfeld-Adams James D JD Ficicioglu Can C Yudkoff Mark M Enns Gregory M GM Lichter-Konecki Uta U Gallagher Renata R Tuchman Mendel M

Translational science of rare diseases 20181220 3-4

Organic acidemias and urea cycle disorders are ultra-rare inborn errors of metabolism characterized by episodic acute decompensation, often associated with hyperammonemia, resulting in brain edema and encephalopathy. Retrospective reports and translational studies suggest that N-carbamylglutamate (NCG) may be effective in reducing ammonia levels during acute decompensation in two organic acidemias, propionic and methylmalonic acidemia (PA and MMA), and in two urea cycle disorders, carbamylphosph ...[more]

PMID: 30613471

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Dataset Information

Conducting an investigator-initiated randomized double-blinded intervention trial in acute decompensation of inborn errors of metabolism: Lessons from the N-Carbamylglutamate Consortium.

Publications

Conducting an investigator-initiated randomized double-blinded intervention trial in acute decompensation of inborn errors of metabolism: Lessons from the N-Carbamylglutamate Consortium.

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