Efficacy of Open-Label Placebo, Double-Blind Placebo, and Peppermint Oil in IBS

R01AT008573

R01AT008573 Lembo, Anthony (contact PI) Project Summary/Abstract Irritable bowel syndrome (IBS) affects 7-15% of the population in North America and results in high health care utilization costs. Despite the heavy disease burden of IBS, few therapies have been proven safe and widely effective. In a previous large (N=262) randomized controlled trial (RCT), our team showed that IBS can be successfully treated with blinded placebo. Our team has also shown in a recent RCT (N=80) that open-label placebo pills can result in statistically and clinically significant improvements in IBS symptoms compared to a no treatment control group. Furthermore, we recently completed a survey of 853 patients and found that >60% would be willing to be treated for chronic abdominal pain with open-label placebo. To follow up on these studies, the current application seeks to determine whether blinding (i.e., open-label vs. double-blind) affects the efficacy of placebo compared to no treatment control. We propose a 6-week RCT with 280 IBS patients on standard treatment for IBS who will be randomly assigned to one of five arms (A) open-label placebo (n=70), (B) double-blind placebo (n=70), (C) open-label peppermint oil (n=35), (D) double-blind peppermint oil (n=35), and (E) no treatment control (n=70). Groups A, B, C, and D comprise a 2x2 factorial design, to which we have added a no treatment control (E). Given that the study primarily concerns placebo effects and peppermint oil is being used as a control, patients will be assigned to placebo vs peppermint in a 2:1 ratio. This design will allow us to examine a number of questions in the treatment of IBS that are critical to both practice and research design, including: (1) Is open-label placebo more effective than no treatment control? (2) Are open-label treatments more effective than double-blind treatments? Secondary questions include: 1) Does the difference in abdominal cramps, a symptom associated with IBS, between peppermint oil and placebo vary depending on whether treatments are delivered open-label or double-blind?; (2) Confirming our previous findings that the COMT val158met polymorphisms predict placebo response in IBS; (3) Replicating our previous finding that the psychological traits of extraversion, agreeableness, and openness are associated with placebo response in IBS. We will also perform a nested “in-depth” qualitative study (N=50) to assess patients’ experiences.