Efficacy and Safety of Peppermint Oil in a Randomized Double-blind Trial of Patients With Irritable Bowel Syndrome
Weerts, Zsa Zsa R. M.; Masclee, Ad A. M.; Witteman, Ben J. M.; Clemens, Cees H. M.; Winkens, Bjorn; Brouwers, Jacobus R. B. J.; Frijlink, Henderik W.; Muris, Jean W. M.; De Wit, Niek J.; Essers, Brigitte A. B.; Tack, Jan; Snijkers, Johanna T. W.; Bours, Andrea M. H.; de Ruiter-van der Ploeg, Annieke S.; Jonkers, Daisy M. A. E.; Keszthelyi, Daniel
(2020) Gastroenterology, volume 158, issue 1, pp. 123 - 136
(Article)
Abstract
Background & Aims: Peppermint oil is frequently used to treat irritable bowel syndrome (IBS), despite a lack of evidence for efficacy from high-quality controlled trials. We studied the efficacy and safety of small-intestinal–release peppermint oil in patients with IBS and explored the effects of targeted ileocolonic-release peppermint oil. Methods: We
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performed a double-blind trial of 190 patients with IBS (according to Rome IV criteria) at 4 hospitals in The Netherlands from August 2016 through March 2018; 189 patients were included in the intent-to-treat analysis (mean age, 34.0 years; 77.8% female; 57.7% in primary care), and 178 completed the study. Patients were randomly assigned to groups given 182 mg small-intestinal–release peppermint oil, 182 mg ileocolonic-release peppermint oil, or placebo for 8 weeks. The primary endpoint was abdominal pain response, as defined by the US Food and Drug Administration: at least a 30% decrease in the weekly average of worst daily abdominal pain compared with baseline in at least 4 weeks. The co-primary endpoint was overall relief of IBS symptoms, as defined by the European Medicines Agency. Secondary endpoints included abdominal pain, discomfort, symptom severity, and adverse events. Results: Abdominal pain response did not differ significantly between the peppermint oil and placebo groups: 29 of 62 patients in the small-intestinal–release peppermint oil group had a response (46.8%, P =. 170 vs placebo), 26 of 63 patients in the ileocolonic-release peppermint oil group had a response (41.3%, P =. 385 vs placebo), and 22 of 64 patients in the placebo group had a response (34.4%). We did not find differences among the groups in overall relief (9.7%, P =. 317 and 1.6%, P =. 351 vs 4.7% for placebo). The small intestinal peppermint oil did, however, produce greater improvements than placebo in secondary outcomes of abdominal pain (P =. 016), discomfort (P =. 020), and IBS severity (P =. 020). Adverse events, although mild, were more common in both peppermint oil groups (P <. 005). Conclusions: In a randomized trial of patients with IBS, we found that neither small-intestinal–release nor ileocolonic-release peppermint oil (8 weeks) produced statistically significant reductions in abdominal pain response or overall symptom relief, when using US Food and Drug Administration/European Medicines Agency recommended endpoints. The small-intestinal–release peppermint oil did, however, significantly reduce abdominal pain, discomfort, and IBS severity. These findings do not support further development of ileocolonic-release peppermint oil for treatment of IBS. Clinicaltrials.gov, Number: NCT02716285.
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Keywords: Functional Gastrointestinal Disorder, PERSUADE Study, RCT, Treatment, Gastroenterology, Hepatology, Journal Article
ISSN: 0016-5085
Publisher: W.B. Saunders Ltd
Note: Funding Information: Funding Funding for this study was provided by a grant received from ZonMw (The Netherlands Organisation for Health Research and Development [Dutch government]), grant number 836031017. The study was initiated by the academic authors in collaboration with WillPharma SA, Wavre, Belgium. The independent ZonMw subsidizing committee, advised by external referees, had input in the study design. The peppermint oil capsules for this study have been provided in kind by Will Pharma SA, Wavre, Belgium. In addition, Will Pharma SA provided funding for the execution of the phase 1 study (Adv Ther 2018;35:1965–1978; https://doi.org/10.1007/s12325-018-0802-1), the execution of which was a prerequisite for receiving funding for the current study from ZonMw. The study design, data collection, analysis, and interpretation were done by the academic authors without industry involvement. The decision to submit was made by the academic authors with no restrictions imposed by the sponsor. WillPharma SA was provided the opportunity to review the manuscript before publication, but the content of the manuscript was at the sole discretion of the academic authors. Conflicts of interest These authors disclose the following: Ad A. M. Masclee and Daniel Keszthelyi have received a ZonMw (The Netherlands Organisation for Health Research and Development [Dutch government]), health care efficiency grant for the execution of this study. Ad A. M. Masclee and Daniel Keszthelyi have received an unrestricted research grant from Will Pharma SA, which also supported Zsa Zsa R. M. Weerts to attend a scientific meeting. Ad A. M. Masclee and Daniel Keszthelyi have received research funding from Allergan and Grünenthal (both unrelated to the current study). Ad A. M. Masclee has given scientific advice to Bayer and Kyowa Kirin and has received funding from PENTAX Europe GmbH. Daniel Keszthelyi has given scientific advice to Biocodex and Bayer. The employer of Daniel Keszthelyi and Ad A. M. Masclee has an agreement with Will Pharma SA regarding the exploitation of a potential market authorization of the ileocolonic formulation of peppermint oil for irritable bowel syndrome. Jacobus R. B. J. Brouwers has received a consultancy fee from Will Pharma SA. The employer of Henderik W. Frijlink has a license agreement with Will Pharma SA regarding the ColoPulse technology. Jan Tack has given scientific advice to Alfa Wassermann, Allergan, Christian Hansen, Danone, Grünenthal, Ironwood, Janssen, Kyowa Kirin, Menarini, Mylan, Neutec, Novartis, Noventure, Nutricia, Shionogi, Shire, Takeda, Theravance, Tramedico, Tsumura, Zealand, and Zeria Pharmaceutical and has served on the speakers bureau for Abbott, Allergan, AstraZeneca, Janssen, Kyowa Kirin, Menarini, Mylan, Novartis, Shire, Takeda, and Zeria. Annieke S. de Ruiter-van der Ploeg has received financial support from Allergan to attend a scientific meeting. The remaining authors disclose no conflicts. Publisher Copyright: © 2020 AGA Institute
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