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The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome
  1. Tamira K Klooker1,
  2. Breg Braak1,
  3. Karin E Koopman1,
  4. Olaf Welting1,
  5. Mira M Wouters2,
  6. Sicco van der Heide3,
  7. Michael Schemann4,
  8. Stephan C Bischoff5,
  9. Rene M van den Wijngaard1,
  10. Guy E Boeckxstaens1,2
  1. 1Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
  2. 2Department of Gastroenterology, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
  3. 3Laboratory of Allergy and Pulmonary Diseases, University Medical Centre, Groningen, The Netherlands
  4. 4Department of Human Biology, TU Munich, Freising, Germany
  5. 5Department of Nutritional Medicine and Immunology, University of Hohenheim, Stuttgart, Germany
  1. Correspondence to Professor Dr G E Boeckxstaens, Department of Gastroenterology, University Hospital Leuven, Catholic University of Leuven, Herestraat 45, Leuven 3000, Belgium; guy.boeckxstaens{at}med.kuleuven.be

Abstract

Background Mast cell activation is thought to be involved in visceral hypersensitivity, one of the main characteristics of the irritable bowel syndrome (IBS). A study was therefore undertaken to investigate the effect of the mast cell stabiliser ketotifen on rectal sensitivity and symptoms in patients with IBS.

Methods 60 patients with IBS underwent a barostat study to assess rectal sensitivity before and after 8 weeks of treatment. After the initial barostat, patients were randomised to receive ketotifen or placebo. IBS symptoms and health-related quality of life were scored. In addition, mast cells were quantified and spontaneous release of tryptase and histamine was determined in rectal biopsies and compared with biopsies from 22 age- and gender-matched healthy volunteers.

Results Ketotifen but not placebo increased the threshold for discomfort in patients with IBS with visceral hypersensitivity. This effect was not observed in normosensitive patients with IBS. Ketotifen significantly decreased abdominal pain and other IBS symptoms and improved quality of life. The number of mast cells in rectal biopsies and spontaneous release of tryptase were lower in patients with IBS than in healthy volunteers. Spontaneous release of histamine was mostly undetectable but was slightly increased in patients with IBS compared with healthy volunteers. Histamine and tryptase release were not altered by ketotifen.

Conclusions This study shows that ketotifen increases the threshold for discomfort in patients with IBS with visceral hypersensitivity, reduces IBS symptoms and improves health-related quality of life. Whether this effect is secondary to the mast cell stabilising properties of ketotifen or H1 receptor antagonism remains to be further investigated.

Trial Registration Number NTR39, ISRCTN22504486.

  • Irritable bowel syndrome
  • visceral hypersensitivity
  • mast cell
  • tryptase
  • histamine
  • ketotifen
  • functional bowel disorder

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Footnotes

  • Funding TKK is supported by a grant from the Netherlands Digestive Diseases Foundation (MLDS) grant number MWO 05-42 and by a grant from Johnson and Johnson. GEB is funded by the European Seventh Framework Programme Theme (Health-2007-2.4.5-2, IPODD) and by a grant from the Flemish Government (Odysseus program, Fonds Wetenschappelijk Onderzoek (FWO), grant G.0905.08). The funders had no influence on the study design or on the collection, analysis, interpretation of data; on the writing of the report; or on the decision to submit the paper for publication.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Medical Ethics Committee of the Academic Medical Center Amsterdam.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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