- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03793790
The Role of Learning in Nocebo Hyperalgesia
Learning Mechanisms in Nocebo Hyperalgesia: the Role of Conditioning and Extinction Processes
Study Overview
Status
Conditions
Detailed Description
Main planned analyses:
Primary Outcome; Comparing the effectivity of conditioning with PRF, conditioning with CRF, and sham conditioning, in inducing nocebo effects on pain:
The magnitude of the induced nocebo effect during the first evocation phase (dependent variable), will be compared between induction groups (independent variable). The pain ratings for the first control trial will be measured against the pain ratings for the first reinforced trial, yielding the magnitude of the nocebo effect. A 3x2 mixed model Analysis of Variance (ANOVA) will be used, treating group as the between-subjects factor with three levels (PRF, CRF, sham) and magnitude of the nocebo effect on pain as a within-subjects measure with two levels (first control and first reinforced trial). Planned contrasts will be conducted.
Secondary Outcome; Comparing the effectivity of counterconditioning and extinction in attenuating nocebo effects on pain:
The nocebo effect still present in the second evocation phase (dependent variable) will be compared between attenuation groups (independent variable). This effect will be measured as the change in pain ratings reported in the first reinforced trial of the first evocation phase (after induction) and pain ratings reported in the first reinforced trial of the second evocation phase (after attenuation). This effect will be further analysed by measuring any change in pain reports for the control trials (second dependent variable) in the same way. The effect of induction group will also be further explored. A 2x2 mixed model ANOVA will be conducted, with attenuation group as the between-subjects factor (counterconditioning and extinction) and the degree to which the nocebo effect has been attenuated as the within-subjects measure with two levels (first and second evocation phase for the first reinforced trials). Further secondary analyses will be conducted.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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South Holland
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Leiden, South Holland, Netherlands, 2333 AL
- Leiden University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Aged 18 - 35 years
- Good understanding of the Dutch language
Exclusion Criteria:
- Severe or chronic physical morbidity (e.g., heart and lung diseases, diabetes)
- Psychiatric disorders (DSM diagnosis; e.g., depression, autism)
- Chronic pain complaints (≥ 6 months) at present or in the past
- Current pain
- Current use of analgesic medication
- Pregnancy
- After inclusion, participants who do not reach a sensation of high pain with the highest temperature administered or participants who appear unable to distinguish between moderate and high pain stimuli will also be excluded
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group 1
Conditioning nocebo effects on pain with a partial reinforcement schedule (induction) and counterconditioning of the previously induced nocebo effect (attenuation).
|
Conditioning with partial reinforcement (PRF) provides an uncertain pairing of unconditioned high pain stimuli and conditioned stimuli (i.e., on-screen messages signaling the activation of a mock medical device).
During PRF only 70 percent of unconditioned stimuli are paired to conditioned stimuli.
Pain of only moderate intensity is used for control stimuli that are paired to the deactivation of the mock device and are also used in the 30 percent of unreinforced trials.
During counterconditioning, the previously conditioned nocebo effects on pain are attenuated by pairing the same conditioned stimuli (i.e., on-screen messages signaling the activation of a mock medical device) to thermal pain stimuli of low intensity.
|
Experimental: Group 2
Conditioning nocebo effects on pain with a partial reinforcement schedule (induction) and extinction of the previously induced nocebo effect (attenuation).
|
Conditioning with partial reinforcement (PRF) provides an uncertain pairing of unconditioned high pain stimuli and conditioned stimuli (i.e., on-screen messages signaling the activation of a mock medical device).
During PRF only 70 percent of unconditioned stimuli are paired to conditioned stimuli.
Pain of only moderate intensity is used for control stimuli that are paired to the deactivation of the mock device and are also used in the 30 percent of unreinforced trials.
During extinction, the previously conditioned nocebo effects on pain are attenuated by pairing the same conditioned stimuli (i.e., on-screen messages signaling the activation of a mock medical device) only to control stimuli of moderate intensity (previously paired to the deactivation of the mock device).
|
Experimental: Group 3
Conditioning nocebo effects on pain with a continuous reinforcement schedule (induction) and counterconditioning of the previously induced nocebo effect (attenuation).
|
During counterconditioning, the previously conditioned nocebo effects on pain are attenuated by pairing the same conditioned stimuli (i.e., on-screen messages signaling the activation of a mock medical device) to thermal pain stimuli of low intensity.
During conditioning with continuous reinforcement (CRF) unconditioned high pain stimuli are paired to conditioned stimuli (i.e., on-screen messages signaling the activation of a mock medical device) in 100 percent of conditioning trials.
Pain of only moderate intensity is used for control stimuli that are paired to the deactivation of the mock device.
|
Experimental: Group 4
Conditioning nocebo effects on pain with a continuous reinforcement schedule (induction) and extinction of the previously induced nocebo effect (attenuation).
|
During extinction, the previously conditioned nocebo effects on pain are attenuated by pairing the same conditioned stimuli (i.e., on-screen messages signaling the activation of a mock medical device) only to control stimuli of moderate intensity (previously paired to the deactivation of the mock device).
During conditioning with continuous reinforcement (CRF) unconditioned high pain stimuli are paired to conditioned stimuli (i.e., on-screen messages signaling the activation of a mock medical device) in 100 percent of conditioning trials.
Pain of only moderate intensity is used for control stimuli that are paired to the deactivation of the mock device.
|
Sham Comparator: Group 5
Sham conditioning of nocebo effects on pain (induction) and extinction (attenuation).
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In the sham group, participants receive different instructions (namely, that the activation of the device is not expected to affect their pain sensitivity).
Additionally, during sham conditioning unconditioned stimuli are not consistently paired to conditioned stimuli, thereby preventing the formation of an association between high pain stimuli and the activation of the mock medical device.
In the attenuation phase participants undergo an extinction procedure.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Magnitude of nocebo effects on pain (rated on a 0-10 numeric rating scale) after PRF, CRF, or sham conditioning.
Time Frame: Testing day 1, in the 1st evocation phase
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This will be calculated in the first evocation phase, by analysing the pain ratings for the first reinforced trial against the pain ratings for the first control trial.
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Testing day 1, in the 1st evocation phase
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Magnitude of nocebo effects on pain (rated on a 0-10 numeric rating scale) still present after counterconditioning or extinction.
Time Frame: Testing day 1, in the 2nd evocation phase
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This will be calculated by analysing the pain ratings for the first reinforced trial in the second evocation phase against the pain ratings for the first reinforced trial in the first evocation phase.
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Testing day 1, in the 2nd evocation phase
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Possible resistance to extinction of induced nocebo effects on pain (rated on a 0-10 numeric rating scale) after PRF as compared to after CRF.
Time Frame: Testing day 1, in the attenuation phase and the 2nd evocation phase
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Exploring whether participants in the PRF group will exhibit higher resistance to extinction during attenuation, as compared to participants in the CRF group.
This will be assessed by analyzing the time-course of extinction of the previously induced nocebo effects on pain (rated on a 0-10 numeric rating scale) during the attenuation phase and the 2nd evocation phase
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Testing day 1, in the attenuation phase and the 2nd evocation phase
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Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CEP18-0816/318
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ANALYTIC_CODE
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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