?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.
Substantial research evidence now exists to indicate that placebos can have powerful clinical and research effects; however, most clinicians and researchers believe that either deception or concealment is necessary to achieve a placebo response. A critical question addressed by this proposal is whether placebo effects can be directly and ethically harnessed in IBS with an 'honest' placebo. Furthermore, this proposal also tests the highly clinically relevant question of whether peppermint oil, a medication purported to provide significant relief of IBS symptoms but not previously studied in the United States, is superior to placebo in treating IBS.
