Data_Sheet_3_Boosting open-label placebo effects in acute induced pain in healthy adults (BOLPAP-study): study protocol of a randomized controlled trial.pdf

IntroductionPain 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 analysisThis 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.
DiscussionThis 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 disseminationThe “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 RegistrationThis study is registered at ClinicalTrials.gov (NCT05819476) and is listed in the Swiss National Registry at kofam.ch (SNCTP000005470).

引言：疼痛是临床医疗场景中高发生率的症状，现有治疗手段仍十分有限。以合乎伦理的方式利用安慰剂效应，可为临床实践中的疼痛管理提供全新解决方案。已有研究证实，开放标签安慰剂（open-label placebos, OLP）可显著缓解急性疼痛，但在临床推广应用前，仍需进一步明确该类安慰剂的相关特性。本研究旨在评估开放标签安慰剂的镇痛效应持续时长，并探索增强该镇痛效应的可行性。

研究方法与方案：本研究为一项正在进行中的单中心随机对照试验（首例受试者于2023年3月入组）的研究方案，试验分为两个子研究以探索开放标签安慰剂的应用效果。两个子研究均采用皮内电刺激模型对健康成年受试者诱发疼痛。第一子研究的受试者将接受两次访视：一次为干预访视，受试者将接受一次开放标签安慰剂注射并辅以基于循证医学依据的治疗原理说明；另一次为无任何干预的对照访视。第二子研究的受试者将被随机分为三组：① 固定时间强化组：在预设时间点追加一次开放标签安慰剂注射；② 按需强化组：根据受试者需求追加一次开放标签安慰剂注射；③ 对照组：仅接受一次开放标签安慰剂注射。研究将采用两独立样本t检验分析不同时间点的疼痛评分（采用数字疼痛评分量表（Numeric Rating Scale, NRS））的组间差异。第二子研究中固定时间强化组的追加注射时间点，将通过第一子研究的数据结合分段混合效应模型等统计方法确定。

讨论：本研究旨在进一步明确开放标签安慰剂的镇痛效应特征，可为后续将其应用于临床实践提供关键依据，助力多模式镇痛理念的落地实施。

伦理与成果传播：本研究方案已获瑞士西北与中部伦理委员会（Ethikkommission Nordwest- und Zentralschweiz，BASEC 2023-00296）批准。研究分析结果将投稿至同行评议期刊发表。

临床试验注册：本研究已在ClinicalTrials.gov（注册号：NCT05819476）注册，并同时收录于瑞士国家临床试验注册平台kofam.ch（注册号：SNCTP000005470）。