Original ResearchFull Report: Clinical—Alimentary TractEfficacy and Safety of Peppermint Oil in a Randomized, Double-Blind Trial of Patients With Irritable Bowel Syndrome
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Section snippets
Study Design, Setting, and Patients
The PEppeRmint Oil for the treatment of Irritable Bowel Syndrome: optimizing therapeUtic strAtegies using targeted DElivery (PERSUADE) study was a randomized, double-blind, placebo-controlled trial and was performed in 4 Dutch hospitals: 1 academic with a combined secondary and tertiary care function (Maastricht University Medical Center+ [MUMC+]) and 3 secondary care hospitals (Hospital Gelderse Vallei, Ede; Alrijne Hospital, Leiden; and Medical Center Leeuwarden). The study protocol was
Patient Disposition, Demographics, and Baseline Characteristics
Between August 2016 and March 2018, 622 patients were screened for participation in this study, of whom 190 were randomized (Supplementary Figure 2). One patient was erroneously randomized (ie, without having a mean worst abdominal score of more than 3 during the pretreatment period) and was excluded from further analyses. Therefore, the modified ITT population consisted of 189 patients. Baseline characteristics are shown in Table 1 and were balanced across treatment groups (mean overall age,
Discussion
To our knowledge, this is the first randomized, double-blind, placebo-controlled clinical trial of peppermint oil in patients with Rome IV-defined IBS. It showed that neither small-intestinal–release nor ileocolonic-release peppermint oil led to a statistically significant reduction in abdominal pain or increase in global relief based on the prespecified primary outcome measures as defined by FDA and EMA guidelines. Small-intestinal–release, but not ileocolonic, peppermint oil, however, did
Acknowledgments
We thank all patients with IBS who participated in the PERSUADE study; N. C. P. Aendekerk, D. J. P. A. Janssen, A. B. A. Quanjel, G. Van Hooff, G. L. Homans, A. J. Van de Vendel, M. G. Oosterveer, A. Westendorp-Ijdema, L. Vork, H. J. A. Jebbink, and G. J. Tack-Blokker for their practical assistance and help with recruitment during the study; the Dutch IBS Patient Federation for its cooperation; MEMIC (the center for data and information management at MUMC+) for the development of the electronic
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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.
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.
Author names in bold designate shared co-first authorship.