title: Enteric-release glyceryl trinitrate in active Crohn's disease: a randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Mucosal ischaemia may contribute to the pathogenesis of Crohn's disease. Microvascular abnormalities have been found in colonic resection specimens, and mucosal levels of constitutive nitric oxide synthase are reduced.
  
  
  OBJECTIVE
  To assess the efficacy of a novel, enteric-release formulation of the nitric oxide donor, glyceryl trinitrate, aimed at increasing the mucosal circulation and relaxing smooth muscle in the affected bowel.
  
  
  METHODS
  The trial was randomized, double-blind and placebo-controlled. Baseline disease activity was assessed by a structured symptom diary, with blood tests and a quality of life assessment. Patients with a Crohn's disease activity index of > or = 150 and < 450 were randomized to receive 12 weeks of either glyceryl trinitrate (initially 6 mg twice daily, increasing to 9 mg twice daily after 6 weeks) or an identical placebo. Assessments were repeated at 6 and 12 weeks.
  
  
  RESULTS
  Seventy patients (22 male) entered the study; 34 were given glyceryl trinitrate and 36 placebo. At 12 weeks, there were no differences between the treatment groups in terms of Crohn's disease activity index, pain, stool frequency, inflammatory markers or quality of life scores.
  
  
  CONCLUSIONS
  Enteric-release glyceryl trinitrate did not benefit patients with mild to moderately active Crohn's disease. Whilst ischaemia may contribute to the pathogenesis of Crohn's disease, our results fail to provide supportive evidence for this hypothesis.
authors.affiliation: Department of Gastroenterology, University Hospital of Wales, Cardiff, UK.
authors.forename: N D
authors.initials: ND
authors.lastname: Hawkes
authors.forename: C
authors.initials: C
authors.lastname: Richardson
authors.forename: C L
authors.initials: CL
authors.lastname: Ch'Ng
authors.forename: J T
authors.initials: JT
authors.lastname: Green
authors.forename: B K
authors.initials: BK
authors.lastname: Evans
authors.forename: J
authors.initials: J
authors.lastname: Williams
authors.forename: P
authors.initials: P
authors.lastname: Rhodes
authors.forename: J
authors.initials: J
authors.lastname: Rhodes
authors.forename: G L
authors.initials: GL
authors.lastname: Swift
authors.forename: G A
authors.initials: GA
authors.lastname: Thomas
authors.forename: A B
authors.initials: AB
authors.lastname: Hawthorne
authors.forename: J G
authors.initials: JG
authors.lastname: Kingham
authors.forename: J F
authors.initials: JF
authors.lastname: Mayberry
mesh_terms: D000284:Administration, Oral; D000328:Adult; D003424:Crohn Disease / Q000188:drug therapy*; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D005483:Flushing / Q000139:chemically induced; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D005996:Nitroglycerin / Q000009:adverse effects / Q000627:therapeutic use*; D013608:Tablets, Enteric-Coated / Q000008:administration & dosage; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D013608:Tablets, Enteric-Coated; D014665:Vasodilator Agents; D005996:Nitroglycerin