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Chapter 7 144 channels on sensory afferents. 8 We therefore hypothesized that a higher exposure of the colonic afferents through targeted ileocolonic delivery of peppermint oil would enhance antinociceptive effects and thereby improve efficacy. In addition, small-intestinal release peppermint oil therapy is often discontinued due to mild, but burdensome upper gastrointestinal (GI) adverse events (AEs) that are assumed to be related to the relaxation of the lower esophageal sphincter 26 and can hamper therapy adherence. We therefore also postulated that the ileocolonic release formulation would decrease these AEs. Materials and methods Study design, setting, and patients The PE ppe R mint Oil for the treatment of Irritable Bowel S yndrome: optimizing therape U tic str A tegies using targeted DE livery (PERSUADE) study was a randomized, double-blind, placebo-controlled trial and was performed in four Dutch hospitals: one academic with a combined secondary and tertiary care function (Maastricht University Medical Center+ (MUMC+)), and three secondary care (Hospital Gelderse Vallei, Ede; Alrijne Hospital, Leiden; Medical Center Leeuwarden). The study protocol had been approved by the MUMC+ Ethics Committee (applicable to all centers). All study procedures were performed in compliance with Good Clinical Practice Guidelines and according to the revised Declaration of Helsinki. All subjects gave written informed consent prior to participation. All authors had access to the study data and reviewed and approved the final manuscript. Patients, between 18 and 75 years of age, fulfilling the Rome IV criteria for IBS, without alarm symptoms, were recruited via primary care, via the outpatient clinics of the above-mentioned hospitals, or via self-referral through public advertisements, social media, and the Dutch IBS patient federation. Detailed in- and exclusion criteria are given in the Supplementary Material . Patients were screened for eligibility in a prescreening (telephone interview) and a medical screening that included history taking and a physical examination. After the screening, eligible patients entered a 14-days pre-treatment period during which they scored their daily worst abdominal pain in a digital symptom diary (scored on an 11-point numerical-rating-scale (NRS), 0=no pain, 10=worst possible pain). Subsequently, those with a mean worst abdominal score of at least 3 were then randomized to 182 mg of small-intestinal release peppermint oil (Tempocol, WillPharma S.A.), 182 mg of ileocolonic release peppermint oil (Tempocol, core-