title: A randomized placebo-controlled trial of miglustat in cystic fibrosis based on nasal potential difference.
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.
authors.affiliation: Pediatric Pulmonology & Cystic Fibrosis Unit, Cliniques St Luc, Université catholique de Louvain, 10 Avenue Hippocrate, 1200 Brussels, Belgium. anissa.leonard@uclouvain.be
authors.forename: Anissa
authors.initials: A
authors.lastname: Leonard
authors.forename: Patrick
authors.initials: P
authors.lastname: Lebecque
authors.forename: Jasper
authors.initials: J
authors.lastname: Dingemanse
authors.forename: Teresinha
authors.initials: T
authors.lastname: Leal
mesh_terms: D017485:1-Deoxynojirimycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002648:Child; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D005500:Follow-Up Studies; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D017485:1-Deoxynojirimycin; D012965:Sodium Chloride; C059896:miglustat