ABSTRACT
Introduction: Pain is a highly prevalent symptom in the hospital setting, but treatment options remain limited. Harnessing the placebo effect in an ethical manner could provide a new possibility to reduce pain in clinical practice. So called open-label placebos (OLP) have been shown to elicit significant effects in reducing acute pain. But, before implementation, more knowledge concerning the properties of OLPs is needed. This study aims to assess the duration of analgesic effects from OLP and to determine the possibility of boosting such effects. Methods and analysis: This is the protocol of an ongoing (first patient enrolled in March 2023) single-site randomized trial investigating OLPs in two parts (i.e., substudies). In both parts, pain will be induced in healthy adults using an intradermal electrical stimulation model. Participants in Part 1 will have two study visits: An interventional visit with one OLP injection accompanied by an evidence-based treatment rationale and a control visit with no treatment. For Part 2, participants will be randomized into three groups: (1) A fixed-time "Booster" group including one single repetition of the OLP injection at a fixed time point, (2) an on-demand "Booster" group including one single repetition of the OLP injection on-demand, and (3) a control group who will receive just one OLP injection. Differences in pain ratings over time (using the Numeric Rating Scale) will be analyzed with several two-sample t-tests. The time point for a fixed-time "Booster" in Part 2 will be derived from Part 1 with additional statistical tools such as a broken-stick mixed-effect model. Discussion: This study aims to further characterize the analgesic effects of OLPs. In doing so, it will provide valuable information needed for later implementation of OLPs in clinical practice, where they could play a role in multimodal analgesic concepts. Ethics and dissemination: The "Ethikkommission Nordwest- und Zentralschweiz" (BASEC 2023-00296) approved the study protocol. Results of the analysis will be submitted for publication in a peer-reviewed journal. Clinical Trial Registration: This study is registered at ClinicalTrials.gov (NCT05819476) and is listed in the Swiss National Registry at kofam.ch (SNCTP000005470).
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).
