A randomized placebo-controlled trial of miglustat in cystic fibrosis based on nasal potential difference

J Cyst Fibros. 2012 May;11(3):231-6. doi: 10.1016/j.jcf.2011.12.004. Epub 2012 Jan 27.

Abstract

Background: Preclinical data suggest that miglustat could restore the function of the cystic fibrosis transmembrane conductance regulator gene in cystic fibrosis cells.

Methods: Single-center, randomized, double-blind, placebo-controlled, crossover Phase II study in 11 patients (mean±SD age, 26.3±7.7 years) homozygous for the F508del mutation received oral miglustat 200 mgt.i.d. or placebo for two 8-day cycles separated by a 14-day washout period. The primary endpoint was the change in total chloride secretion (TCS) assessed by nasal potential difference.

Results: No statistically significant changes in TCS, sweat chloride values or FEV(1) were detected. Pharmacokinetic and safety were similar to those observed in patients with other diseases exposed to miglustat.

Conclusions: There was no evidence of a treatment effect on any nasal potential difference variable. Further studies with miglustat need to adequately address criteria for assessment of nasal potential difference.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / administration & dosage
  • 1-Deoxynojirimycin / analogs & derivatives*
  • 1-Deoxynojirimycin / pharmacokinetics
  • Administration, Oral
  • Adolescent
  • Adult
  • Child
  • Cross-Over Studies
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / metabolism
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacokinetics
  • Female
  • Follow-Up Studies
  • Glycoside Hydrolase Inhibitors
  • Humans
  • Male
  • Nasal Mucosa / drug effects*
  • Nasal Mucosa / metabolism
  • Sodium Chloride / metabolism
  • Treatment Outcome
  • Young Adult

Substances

  • Enzyme Inhibitors
  • Glycoside Hydrolase Inhibitors
  • 1-Deoxynojirimycin
  • Sodium Chloride
  • miglustat