Zsa Zsa Weerts

Chapter 7 160 recruitment strategy may have contributed to this relatively young study population. Nevertheless, the subtype distribution was in line with epidemiological findings in IBS. 45 Future studies are required to ascertain the effect in populations from different geographical regions; a current trial in the USA investigating placebo responses uses a peppermint oil comparator. 46 However, because we have recruited IBS patients from primary, secondary and tertiary care, and via social media accounts of the participating centers, we argue that the current study population is representative for the Dutch IBS population seeking help for their symptoms. Caution is, however, necessary when applying these results to clinical practice as they might only apply to patients who have a certain level of pain symptoms, corresponding to both the Rome IV and the FDA pain entry criteria. Second, blinding of the patients may not have been entirely successful due to the smell and taste of peppermint oil and other recognizable adverse events. We tried to limit a confounding effect through the identical appearance of capsules by over- encapsulation. Third, due to possible power limitations and increase in type I error (multiple testing), secondary endpoint analyses should be considered exploratory. Fourth, the treatment period was relatively short in comparison to other IBS trials, therefore potential benefits from a longer treatment period ( i.e. 12-26 weeks) could not be ascertained. Strengths of the current study include the soundness of the experimental design with compliance to recent guidelines on IBS drug trials and as such, reporting on stringent primary outcomes according to FDA and EMA guidelines and intention-to-treat analyses; the meticulous use of state-of-the-art electronic data capture ensuring data quality and completeness; and a well-characterized patient population comprised of both primary and secondary/tertiary care patients diagnosed according to Rome IV diagnostic criteria for IBS with a low drop-out rate. In summary, peppermint oil compared to placebo was not superior in patients with IBS, when using the pre-specified outcome measures abdominal pain response and global relief of IBS symptoms based on recommendations by the FDA and EMA. We found no benefits of a targeted Ileocolonic release peppermint oil formulation for treatment in IBS. Conventional small-intestinal release peppermint oil did, however, improve secondary outcomes such as abdominal pain, abdominal discomfort, and IBS symptom severity with a minimal adverse event profile and high tolerability. Peppermint oil may thus be considered as a worthwhile treatment option for symptom management in IBS.