Zsa Zsa Weerts

Chapter 7 142 Abstract Introduction 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 performed a double-blind trial of 190 patients with IBS (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 (FDA): 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 (EMA). Secondary endpoints included abdominal pain, discomfort, symptom severity, and adverse events (AEs). Results Abdominal pain response did not differ significantly between groups: 29 of 62 patients in the small-intestinal release peppermint oil group had a response (46.8%, P =0.170 vs placebo), 26 of 63 patients in the ileocolonic release peppermint oil group had a response (41.3%, P =0.385 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 =0.317 and 1.6%, P =0.351 vs 4.7% for placebo). The small-intestinal peppermint oil did, however, produce greater improvements than placebo in secondary outcomes of abdominal pain ( P =0.016), discomfort ( P =0.020), and IBS severity ( P =0.020). AEs, although mild, were more common in both peppermint oil groups ( P <0.005). Conclusions 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 FDA/EMA 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.