Open-Label Placebo Treatment for Acute Postoperative Pain (OLP-POP Study): Study Protocol of a Randomized Controlled Trial

Abstract

Introduction: Open-label placebos have been proposed as way of using long recognized analgesic placebo effects in an ethical manner. Recent evidence shows efficacy of open-label placebos for clinical conditions, but there is need for more research on open-label placebos in acute pain. In the treatment of acute postoperative pain, minimization of opioid related side effects remains one of the key challenges. Therefore, this study aims at investigating the potential of adding unconditioned open-label placebos to treatment as usual as a means of reducing opioid consumption and its related side effects in patients with acute postoperative pain.Methods and Analysis: This is the protocol of an ongoing single site randomized controlled trial. The first patient was enrolled in May 2020. In total, 70 patients suffering from acute postoperative pain following dorsal lumbar interbody fusion are randomized to either a treatment as usual group or an experimental intervention group. The treatment as usual group consists of participants receiving a patient-controlled morphine pump. On day 1 and 2 post-surgery, patients in the intervention group receive, in addition to treatment as usual, two open-label placebo injections per day along with an evidence-based treatment rationale explaining the mechanisms of placebos. The primary outcome is measured by means of self-administered morphine during day 1 and 2 post-surgery. Several other outcome measures including pain intensity and adverse events as well as potential predictors of placebo response are assessed. Analysis of covariance will be used to answer the primary research question and additional statistical techniques such as generalized linear mixed models will be applied to model the temporal course of morphine consumption.Discussion: This study will provide valuable insights into the efficacy of open-label placebos in acute pain and will potentially constitute an important step toward the implementation of open-label placebos in the clinical management of acute postoperative pain. In addition, it will shed light on a cost-efficient and patient-centered strategy to reduce opioid consumption and its related side effects, without any loss in pain management efficacy.Ethics and Dissemination: The “Ethikkommission Nordwest- und Zentralschweiz” (BASEC2020-00099) approved the study protocol. Results of the analysis will be submitted for publication in a peer-reviewed journal.Clinical Trial Registration: The study is registered at ClinicalTrials.gov (NCT04339023) and is listed in the Swiss national registry at kofam.ch (SNCTP000003720).

Boosting open-label placebo effects in acute induced pain in healthy adults (BOLPAP-study): study protocol of a randomized controlled trial

“…The placebo effect could be altered in clinical populations with possible interfering variables such as comorbidities [particularly if the cognition is impaired ( 83 )], concomitant medication, (negative) emotions ( 84 ) or deviant procedures [e.g., no sufficient OLP rationale ( 26 )]. In summary, with this study, we strive to find hypotheses concerning OLPs, which can later be translated to and tested in clinical populations ( 32 ).…”

“…The experimental intervention will consist of two components, similar to our former study ( 32 ): a scripted, evidence-based treatment rationale and an OLP injection.…”

“…Two meta-analyses summarize clinical OLP studies and highlight significant effects in various conditions, such as allergic rhinitis, menopausal hot flushes, attention deficit hyperactivity disorder, cancer-related fatigue, irritable bowel syndrome, and chronic low back pain ( 56 , 57 ). Findings on acute pain, though limited, are promising ( 25 – 29 , 32 , 35 , 49 , 55 ). To our knowledge, the effects of OLPs on acute pain-associated phenomena, hyperalgesia and allodynia, have only been investigated in one study thus far ( 55 ).…”