Manipulating NMDA-dependent Learning to Alter Nocebo Effects: A Pharmacological fMRI Study on Pain
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Magnitude of induced nocebo hyperalgesia
研究概览
简要总结
Nocebo effects, negative responses to inert or active treatments which are putatively induced by negative outcome expectations, have been shown to play a significant role in pain perception. The underlying neurobiological mechanisms of these effects remain largely unexplored. The primary objective of this study is to test the role of N-methyl-D-aspartate (NMDA) receptor-dependent learning in an experimental model of conditioned nocebo effects on self-reported pain. Secondary objectives are to examine the role of the NMDA manipulation and related neural correlates during the acquisition and extinction of nocebo effects using statistical learning models. This study will utilize a placebo controlled, double-blind design with respect to the pharmacological administration of 80 mg D-Cycloserine (DCS), an NMDA agonist, or placebo. Validated conditioning and verbal suggestion (VS) paradigms will induce nocebo effects on pain in a random sample of 50 healthy adults. The primary endpoint of the study is the magnitude of the induced nocebo effect on pain measured as the difference between self-reported pain, between the first conditioned and control extinction trials. Secondary endpoints include the classification analysis of the Blood Oxygen Level Dependent (BOLD) responses of participants into pharmacological groups with multivariate pattern analysis. This study will be conducted at Leiden University and the Leiden University Medical Center (LUMC), The Netherlands.
详细描述
Main outcome variable:
- The magnitude of induced nocebo hyperalgesia is defined as the difference in pain ratings for the first nocebo trial compared to the first control trial of the extinction phase.
A significant difference here is assessed within the mixed model analysis of variance (ANOVA), comparing within-subjects differences for control and nocebo trials between DCS and placebo groups.
Time frame: On the day of the experimental session, during the extinction phase
Secondary outcome variables:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged 18 - 35 years
- •Good understanding of the English language
- •Normal or corrected to normal vision
排除标准
- •A potential participant who meets any of the following exclusion criteria will be excluded from participation in this study:
- •History of serious or chronic medical or psychiatric conditions (e.g., convulsions (epilepsy), cardiovascular problems, depression; careful and detailed screening will be carried out for both medical and psychiatric conditions)
- •History of chronic pain or itch conditions
- •Experiencing pain or itch of 1 or more on a 0-10 pain / itch NRS on the day of testing
- •Currently using antihistamines, analgesic medication, or itch-reducing medication (in the 24 hours prior to testing)
- •Use of psychotropic drugs (including recreational drugs such as cannabis and psychotropic prescription-medication; in the past month)
- •Currently being (or intending to become) pregnant, or currently breastfeeding, or planning to father a child in the next 3 months
- •Colour-blindness
- •Body Mass Index under 16 or over 30
- •Meeting any exclusion criteria in the fMRI examination questionnaire which would prohibit fMRI scanning.
- •Having too high of a threshold for pain (where high pain cannot be induced with temperatures lower than 49.5 °C).
研究组 & 干预措施
Augmented learning
Conditioning and extinction of a nocebo response to the activation of a sham electrode, controlled within subjects. All participants in this arm receive a double-blind oral dose of DCS two hours prior to conditioning and fMRI
干预措施: D-cycloserine (Drug)
Augmented learning
Conditioning and extinction of a nocebo response to the activation of a sham electrode, controlled within subjects. All participants in this arm receive a double-blind oral dose of DCS two hours prior to conditioning and fMRI
干预措施: Conditioning (Behavioral)
Augmented learning
Conditioning and extinction of a nocebo response to the activation of a sham electrode, controlled within subjects. All participants in this arm receive a double-blind oral dose of DCS two hours prior to conditioning and fMRI
干预措施: Extinction (Behavioral)
Augmented learning
Conditioning and extinction of a nocebo response to the activation of a sham electrode, controlled within subjects. All participants in this arm receive a double-blind oral dose of DCS two hours prior to conditioning and fMRI
干预措施: fMRI (Other)
Baseline learning
Conditioning and extinction of a nocebo response to the activation of a sham electrode, controlled within subjects. All participants in this arm receive a double-blind oral dose of placebo two hours prior to conditioning and fMRI
干预措施: Conditioning (Behavioral)
Baseline learning
Conditioning and extinction of a nocebo response to the activation of a sham electrode, controlled within subjects. All participants in this arm receive a double-blind oral dose of placebo two hours prior to conditioning and fMRI
干预措施: Extinction (Behavioral)
Baseline learning
Conditioning and extinction of a nocebo response to the activation of a sham electrode, controlled within subjects. All participants in this arm receive a double-blind oral dose of placebo two hours prior to conditioning and fMRI
干预措施: fMRI (Other)
Baseline learning
Conditioning and extinction of a nocebo response to the activation of a sham electrode, controlled within subjects. All participants in this arm receive a double-blind oral dose of placebo two hours prior to conditioning and fMRI
干预措施: Placebo (Drug)
结局指标
主要结局
Magnitude of induced nocebo hyperalgesia
时间窗: Through study completion, an average of 2 weeks
is defined as the difference in pain numerical rating scale ratings (self-report, scale from 0 - no pain to 10 - worst pain imaginable) for the first nocebo trial compared to the first control trial of the extinction phase. A significant difference here is assessed within the mixed model ANOVA, comparing within-subjects differences for the control and nocebo trials between DCS and placebo groups
次要结局
- The difference in blood-oxygen level dependent (BOLD) response at a series of a priori ROIs between pharmacological groups during the acquisition of nocebo effects.(Through study completion, an average of 2 weeks)
- The difference in BOLD response at a series of a priori ROIs between pain at baseline and nocebo-augmented pain.(Through study completion, an average of 2 weeks)
- The classification accuracy (into pharmacological groups), indicating that patterns of activation in the network of a priori ROIs form a model that can detect differences in neural activations during the acquisition of nocebo effects.(Through study completion, an average of 2 weeks)
- The difference in BOLD response at a series of a priori ROIs between pharmacological groups during the extinction of nocebo effects.(Through study completion, an average of 2 weeks)
- The classification accuracy (into pharmacological groups), indicating that patterns of BOLD activation in the network of a priori ROIs form a model that can detect differences in neural activations during the first trials of the extinction phase.(Through study completion, an average of 2 weeks)
- The classification accuracy, indicating that patterns of activation in the network of a priori ROIs form a model that can detect commonalities and differences in neural activations between the experience of pain at baseline and nocebo-augmented pain.(Through study completion, an average of 2 weeks)
- The prediction accuracy, indicating that patterns of activation in the network of a priori ROIs form a model that can predict the magnitude of induced nocebo effects based on patterns of activations during the acquisition of nocebo effects.(Through study completion, an average of 2 weeks)
研究者
AWMEvers
Principal Investigator
Leiden University Medical Center