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

R01AT008573 Lembo，Anthony（联系PI） 项目总结/摘要 肠易激综合征（IBS）影响北美7-15%的人口，并导致高医疗保健利用成本。尽管IBS的疾病负担很重，但很少有治疗方法被证明是安全和广泛有效的。在之前的一项大型（N=262）随机对照试验（RCT）中，我们的研究小组表明，IBS可以用盲态安慰剂成功治疗。我们的团队还在最近的一项随机对照试验（N=80）中表明，与无治疗对照组相比，开放标签安慰剂药丸可以导致IBS症状的统计学和临床显著改善。 此外，我们最近完成了一项对853名患者的调查，发现>60%的患者愿意接受开放标签安慰剂治疗慢性腹痛。为了跟进这些研究，本申请试图确定是否设盲（即，开放标签对双盲）与无治疗对照相比影响安慰剂的功效。我们提出了一项为期6周的随机对照试验，280名接受标准治疗的IBS患者将被随机分配到五个组之一：（A）开放标签安慰剂组（n=70）， (B)双盲安慰剂（n=70），（C）开放标签薄荷油（n=35），（D）双盲薄荷油（n=35），和（E）无治疗对照（n=70）。A、B、C和D组包含2 × 2析因设计，我们在其中添加了无处理对照（E）。 鉴于该研究主要关注安慰剂效应，而薄荷油用作对照，患者将以2：1的比例分配至安慰剂组和薄荷组。这种设计将使我们能够检查IBS治疗中的一些问题，这些问题对实践和研究设计都至关重要，包括：（1）开放标签安慰剂是否比无治疗对照更有效？(2)开放标签治疗比双盲治疗更有效吗？次要问题包括：1）薄荷油和安慰剂之间在腹部绞痛（与IBS相关的症状）方面的差异是否会因治疗是开放标签还是双盲而有所不同？; (2)证实了我们先前的研究结果，即COMT val 158 met多态性预测IBS的安慰剂反应;（3）重复我们先前的研究结果，即外倾性，宜人性和开放性与IBS的安慰剂反应相关。我们还将进行一项嵌套式“深入”定性研究（N=50），以评估患者的经验。

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.