Evaluation of miglustat treatment in patients with type III mucopolysaccharidosis: a randomized, double-blind, placebo-controlled study

J Pediatr. 2011 Nov;159(5):838-844.e1. doi: 10.1016/j.jpeds.2011.04.040. Epub 2011 Jun 12.

Abstract

Objective: To evaluate the efficacy and safety of oral miglustat treatment in patients with mucopolysaccharidosis type III. The primary outcome was efficacy with improvement or stabilization in at least two domains of Vineland Adaptative Behavior Scales at 6 months. The secondary outcome measured the evolution of other cognitive tests at 12 months. The safety and tolerability were assessed throughout the study.

Study design: This was a randomized, double-blind, placebo-controlled, monocenter, institutional, phase IIb to III study. In case of efficacy at 6 months, the study would go on for another 6 months on an open design with all patients receiving miglustat. In the absence of efficacy at 6 months, the trial had to be continued for 6 more months with the initial design.

Results: After 6 months, efficacy was not superior in patients with miglustat. The independent review board confirmed continuing the study until 12 months.

Conclusion: Miglustat treatment was not associated with any improvement/stabilization in behavior problems in patients with mucopolysaccharidosis type III. Miglustat has an acceptable safety profile. However, the study has confirmed that miglustat is able to pass through the blood-brain barrier without significantly decreasing ganglioside levels.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • 1-Deoxynojirimycin / analogs & derivatives*
  • 1-Deoxynojirimycin / blood
  • 1-Deoxynojirimycin / cerebrospinal fluid
  • 1-Deoxynojirimycin / therapeutic use
  • Brain / pathology
  • Child
  • Child, Preschool
  • Cognition / drug effects
  • Double-Blind Method
  • Enzyme Inhibitors / blood
  • Enzyme Inhibitors / cerebrospinal fluid
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Glycoside Hydrolase Inhibitors
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mucopolysaccharidosis III / drug therapy*
  • Neuropsychological Tests
  • Sleep Wake Disorders / drug therapy
  • alpha-Glucosidases / cerebrospinal fluid

Substances

  • Enzyme Inhibitors
  • Glycoside Hydrolase Inhibitors
  • 1-Deoxynojirimycin
  • miglustat
  • alpha-Glucosidases