title: Multicenter phase II randomized study evaluating dose-response of antiperistaltic effect of L-menthol sprayed onto the gastric mucosa for upper gastrointestinal endoscopy.
abstract: OBJECTIVE
  Peppermint oil solution was found to be effective for reducing gastric spasm during upper gastrointestinal endoscopy. The aim of the present study was to assess whether the gastric peristalsis-suppressing effect is dose-dependently induced by L-menthol, the major constituent of peppermint oil, and to determine the recommended dose of an L-menthol preparation.
  
  
  METHODS
  In this phase II, multicenter, double-blind, dose-response study, 131 eligible patients were randomly assigned to receive 20 mL of 0.4% L-menthol (n = 32), 0.8% L-menthol (n = 35), 1.6% L-menthol (n = 30), or placebo (n = 34). The primary efficacy measure was the proportion of subjects with no peristalsis in two time periods, 75 to 105 s after treatment and immediately before the completion of endoscopy.
  
  
  RESULTS
  The peristalsis-suppressing effect of L-menthol increased dose dependently (5.6%, 32.0%, 47.4% and 52.9% in the 0%, 0.4%, 0.8% and 1.6% groups, respectively: P < 0.001, one-tailed Cochran-Armitage trend test). As compared with the placebo group, the proportion of subjects with no peristalsis after administration was significantly higher in the 0.8% group (P = 0.015) and 1.6% group (P = 0.009). Adverse events in the L-menthol dose groups occurred with similar frequencies in the placebo group.
  
  
  CONCLUSIONS
  L-menthol suppresses peristalsis in a dose-dependent manner, and the dose-response reaches a plateau at 0.8% L-menthol. Further Phase III studies are needed to establish the superiority of 0.8% L-menthol over placebo.
authors.affiliation: Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. naoki.hiki@jfcr.or.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiki
authors.forename: Michio
authors.initials: M
authors.lastname: Kaminishi
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Yasuda
authors.forename: Noriya
authors.initials: N
authors.lastname: Uedo
authors.forename: Masumi
authors.initials: M
authors.lastname: Kobari
authors.forename: Terufumi
authors.initials: T
authors.lastname: Sakai
authors.forename: Takashi
authors.initials: T
authors.lastname: Hiratsuka
authors.forename: Kyota
authors.initials: K
authors.lastname: Ohno
authors.forename: Hajime
authors.initials: H
authors.lastname: Honjo
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Nomura
authors.forename: Naohisa
authors.initials: N
authors.lastname: Yahagi
authors.forename: Hisao
authors.initials: H
authors.lastname: Tajiri
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016015:Logistic Models; D008297:Male; D036142:Mentha piperita; D008610:Menthol / Q000008:administration & dosage* / Q000494:pharmacology*; D008875:Middle Aged; D009822:Oils, Volatile / Q000494:pharmacology; D010528:Peristalsis / Q000187:drug effects*; D010938:Plant Oils / Q000494:pharmacology; D055815:Young Adult
chemical_list: D009822:Oils, Volatile; D010938:Plant Oils; D008610:Menthol; C015424:peppermint oil