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

R01AT008573 安东尼·伦博(联系PI) 项目摘要/摘要 肠易激综合征(IBS)影响北美7%-15%的人口，并导致高昂的医疗保健利用成本。尽管IBS的疾病负担很重，但很少有疗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，我们的团队证明了盲用安慰剂可以成功地治疗IBS。我们的团队还在最近的一项随机对照试验(N=80)中表明，与未治疗的对照组相比，开放标签的安慰剂可以在统计和临床上显著改善IBS症状。此外，我们最近完成了对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，目前的应用试图确定与没有治疗对照相比，盲法(即开放标签与双盲)是否影响安慰剂的疗效。我们建议对280名接受IBS标准治疗的IBS患者进行为期6周的随机对照试验，这些患者将被随机分配到五组中的一组(A组)，开放标签安慰剂(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)，(E)无治疗对照组(n=70)。A、B、C和D组包括2x2析因设计，我们在该设计中增加了不处理对照(E)。鉴于这项研究主要涉及安慰剂效应，而薄荷油作为对照，患者将按2：1的比例被分配给安慰剂和薄荷。这一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)开放标签安慰剂比没有治疗对照更有效吗？(2)开放标签治疗比双盲治疗更有效？第二个问题包括：1)薄荷油和安慰剂在腹痛(与IBS相关的症状)方面的差异是否取决于开放标签或双盲治疗？(2)证实了我们之前的发现，即COMT val158met基因多态性可以预测IBS的安慰剂反应；(3)重复我们以前的发现，即外向、随和和开放的心理特征与IBS的安慰剂反应有关。我们还将进行嵌套的“深入”定性研究(N=50)，以评估患者的体验。

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.