Validating a biosignature-predicting placebo pill response in chronic pain in the settings of a randomized controlled trial.
Validating a biosignature-predicting placebo pill response in chronic pain in the settings of a randomized controlled trial.
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在一项随机对照试验的背景下，验证一种预测慢性疼痛中安慰剂药丸反应的生物标记。
DOI：
10.1097/j.pain.0000000000002450
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发表时间：
2022-05-01
期刊：
影响因子：
7.4
通讯作者：
Apkarian AV
中科院分区：
文献类型：
--
作者：
Vachon-Presseau E;Abdullah TB;Berger SE;Huang L;Griffith JW;Schnitzer TJ;Apkarian AV
这项研究的目的是验证一个安慰剂药片反应预测模型-生物签名-将慢性疼痛患者分为安慰剂反应者(预测-PTxResp)和无反应者(预测-PTxNonR)，并测试它是否可以分离安慰剂和积极治疗反应。该模型基于心理和大脑功能的连通性，是在我们之前的研究中得出的，并盲目应用于目前的试验参与者。94例慢性下腰痛(CLBP)患者分为预测-PTxResp或预测-PTxNonR，并随机分为不治疗、安慰剂治疗或萘普生治疗。为了监测疼痛，每天收集两次背部疼痛强度：3周基线，6周治疗，3周冲洗。89名CLBP患者被纳入意向治疗分析，77名CLBP患者被纳入按方案分析。这两项分析都显示了类似的结果。在小组水平上，预测模型表现得非常好，分离了纯粹的安慰剂反应和纯粹的积极治疗反应的单独影响大小，并表明这些影响是相加的。与接受安慰剂或萘普生的预测PTxNonR相比，预测PTxResp的止痛效果约强15%，并且预测PTxNonR成功地隔离了活性药物效应。在单一受试者水平上，生物签名更好地预测了安慰剂无反应者，但准确性较差。生物特征的一个组成部分(背外侧前额叶皮质-中央前回功能连接)可以在三项安慰剂研究和两个不同的队列中推广-CLBP和骨关节炎疼痛患者。这项研究表明，在随机对照试验的背景下，生物签名可以预测群体水平的安慰剂反应。
The objective of this study is to validate a placebo pill response predictive model - a biosignature - that classifies chronic pain patients into placebo-responders (predicted-PTxResp) and non-responders (predicted-PTxNonR), and test whether it can dissociate placebo and active treatment responses. The model, based on psychological and brain functional connectivity, was derived in our previous study and blindly applied to current trial participants. 94 chronic low back pain (CLBP) patients were classified into predicted-PTxResp or predicted-PTxNonR and randomized into no-treatment, placebo treatment, or naproxen treatment. To monitor analgesia, back pain intensity was collected twice a day: 3 weeks baseline, 6 weeks of treatment, 3 weeks of washout. 89 CLBP patients were included in the intent-to-treat analyses and 77 CLBP in the per-protocol analyses. Both analyses showed similar results. At the group level, the predictive model performed remarkably well, dissociating the separate effect sizes of pure placebo response and pure active treatment response, and demonstrating that these effects interacted additively. Pain relief was about 15% stronger in the predicted-PTxResp compared to the predicted-PTxNonR receiving either placebo or naproxen, and the predicted-PTxNonR successfully isolated the active drug effect. At a single subject level, the biosignature better predicted placebo non-responders, with poor accuracy. One component of the biosignature (dorsolateral prefrontal cortex-precentral gyrus functional connectivity) could be generalized across three placebo studies and in two different cohorts - CLBP and osteoarthritis pain patients. This study shows that a biosignature can predict placebo response at a group level in the setting of a randomized controlled trial.
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影响因子：
6.9
作者：
Colloca, Luana;Miller, Franklin G.
通讯作者：
Miller, Franklin G.
影响因子：
5.7
作者：
Berger SE;Vachon-Presseau É;Abdullah TB;Baria AT;Schnitzer TJ;Apkarian AV
通讯作者：
Apkarian AV
影响因子：
3.7
作者：
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通讯作者：
Evers AWM
影响因子：
22.8
作者：
Colloca L;Akintola T;Haycock NR;Blasini M;Thomas S;Phillips J;Corsi N;Schenk LA;Wang Y
通讯作者：
Wang Y
影响因子：
3.6
作者：
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通讯作者：
Babel, Przemyslaw