1. The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome
- Author
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Rene M. van den Wijngaard, Tamira K. Klooker, Breg Braak, Guy Boeckxstaens, Mira M. Wouters, Olaf Welting, Michael Schemann, Karin E. Koopman, Stephan C. Bischoff, Sicco van der Heide, Other departments, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Graduate School, Gastroenterology and Hepatology, Faculteit Medische Wetenschappen/UMCG, and Faculteit der Geneeskunde
- Subjects
Male ,Abdominal pain ,Cell Count ,Gastroenterology ,Histamine Release ,DISEASE ,Irritable Bowel Syndrome ,ACTIVATION ,chemistry.chemical_compound ,Mast Cells ,Irritable bowel syndrome ,biology ,HISTAMINE-RECEPTORS ,Middle Aged ,Mast cell ,medicine.anatomical_structure ,Treatment Outcome ,Sensory Thresholds ,Histamine H1 Antagonists ,Female ,medicine.symptom ,RECTAL DISTENSION ,Histamine ,medicine.drug ,Ketotifen ,Adult ,medicine.medical_specialty ,DISORDERS ,INTOLERANCE ,Tryptase ,Histamine H1 receptor ,ORAL SODIUM CROMOGLYCATE ,Young Adult ,Double-Blind Method ,INFLAMMATION ,Internal medicine ,medicine ,Pressure ,Humans ,HYPERPLASIA ,Aged ,business.industry ,Rectum ,medicine.disease ,Barostat ,DIARRHEA ,Elasticity ,Viscera ,chemistry ,Immunology ,biology.protein ,Quality of Life ,Tryptases ,business - 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 ageand 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.
- Published
- 2010
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