Reducing Nocebo Effects on Pressure Pain
1 other identifier
interventional
69
1 country
1
Brief Summary
Nocebo effects are known to adversely affect the experience of various physical symptoms, such as pain and itch. Nocebo effects can be induced by associative learning mechanisms of classical conditioning. Furthermore, recent studies have shown that counterconditioning can successfully reduce nocebo effects, and to a larger extent than mere extinction, which suggests counterconditioning can be an innovative method for desensitization of symptoms. When using such procedures in clinical practice, deception of patients should be avoided as much as possible. The use of open-label procedures could provide a promising alternative. While previous studies have already shown that open-label placebos are effective, the effects of open-label counterconditioning and closed-label counterconditioning are not extensively investigated in comparison to other strategies, such as extinction, and not yet compared amongst each other. Before implementing such a procedure in clinical practice, it would be relevant to get an insight in the efficacy of both open- and closed-label counterconditioning in healthy participants as compared to extinction and to investigate whether open-label counterconditioning can be equally effective as closed-label counterconditioning. Furthermore, it would be relevant to study the induction and reduction of nocebo effects using a pain modality that mimics the type of pain that people suffering from several chronic pain conditions experience, such as pressure pain. The main aim of the current study is to investigate whether open- and closed-label counterconditioning are more effective in reducing nocebo effects than extinction. To this aim, it will be investigated whether open- and closed-label counterconditioning lead to stronger reductions in nocebo effects on pressure pain than (closed-label) extinction, and whether all three successfully reduce nocebo effects. Finally, it will be tested whether open- and closed label counterconditioning are comparable in effectivity.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable pain
Started Mar 2021
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 23, 2021
CompletedFirst Submitted
Initial submission to the registry
February 17, 2022
CompletedFirst Posted
Study publicly available on registry
March 17, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 5, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
April 5, 2022
CompletedAugust 25, 2022
August 1, 2022
1 year
February 17, 2022
August 24, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Nocebo reduction; group comparison
The change in nocebo effects from after nocebo conditioning (part 1) to after either form of counterconditioning or extinction (part 2) will be compared between groups. The nocebo effect is defined as the difference between the pain scored during experimental trials (on a 0-10 NRS) and during control trials (same NRS). The change is calculated by subtracting the nocebo effect after counterconditioning from the nocebo effect after nocebo conditioning.
On the testing day; testing phase of nocebo induction and reduction
Secondary Outcomes (2)
Nocebo reduction
On the testing day; testing phase of nocebo induction and reduction
Nocebo reduction; equivalence of the two forms of counterconditioning
On the testing day; testing phase of nocebo induction and reduction
Study Arms (3)
Open-label counterconditioning
EXPERIMENTALClosed-label conditioning followed by open-label counterconditioning, using moderately painful stimuli (during conditioning) and non-painful stimuli (during counterconditioning), combined with closed-label nocebo suggestions and open-label nocebo reduction suggestions
Closed-label counterconditioning
EXPERIMENTALClosed-label conditioning followed by closed-label counterconditioning, using moderately painful stimuli (during conditioning) and non-painful stimuli (during counterconditioning), combined with closed-label nocebo suggestions and closed-label nocebo reduction suggestions
Closed-label extinction
ACTIVE COMPARATORClosed-label conditioning followed by closed-label extinction, using moderately painful stimuli (during conditioning) and slightly-painful stimuli (during extinction), combined with closed-label nocebo suggestions during conditioning and no/neutral suggestions during extinction
Interventions
Conditioning consists of a learning and test phase. In the learning phase, a message indicating the sham activation of a Transcutaneous Electrical Nerve Stimulation (TENS) device (CS) will be repeatedly paired with a moderate intensity pressure pain stimulus, whereas a message indicating the deactivation of the sham device will be repeatedly paired with a slightly painful pressure pain stimulus. Participants will be given a verbal suggestion in line with the conditioning procedure (i.e. activation of the device will increase their pain). The testing phase is similar to the learning phase, but a slight pressure pain intensity is used for all trials, to test for a nocebo effect (i.e. to test whether participants score "TENS on" trials as more painful than "TENS off" trials).
Counterconditioning consists of a learning and test phase. In the learning phase, a message indicating the sham activation of the TENS device (CS) is now repeatedly paired with a non-painful intensity pressure pain stimulus, whereas a message indicating the sham deactivation of the TENS device will be repeatedly paired with a slightly painful pressure pain stimulus. Participants will be given a verbal suggestion in line with the counterconditioning procedure (i.e. activation of the device will reduce their pain). The testing phase is similar to the learning phase, but a slight pressure pain intensity is used for all trials, to test whether the nocebo effect is successfully reduced (i.e. to test whether participants no longer score "TENS on" trials as more painful than "TENS off" trials or even score "TENS on" trials as less painful).
Counterconditioning consists of a learning and test phase. In the learning phase, a message indicating the sham activation of the TENS device (CS) is now repeatedly paired with a non-painful intensity pressure pain stimulus, whereas a message indicating the sham deactivation of the TENS device will be repeatedly paired with a slightly painful pressure pain stimulus. Participants will be given a open-label verbal suggestions in line with the counterconditioning procedure (i.e. they are told counterconditioning will be used to reduce nocebo effects and they are told the device is sham, but that their pain will still be influenced because of the placebo effect). The testing phase is similar to the learning phase, but a slight pressure pain intensity is used for all trials, to test whether the nocebo effect is successfully reduced (i.e. to test whether participants no longer score "TENS on" trials as more painful than "TENS off" trials or even score "TENS on" trials as less painful).
Extinction consists of a learning and test phase. In the learning phase, slightly painful stimuli are used for all trials. During the testing phase, again a slight pressure pain intensity is used for all trials, to test whether the nocebo effect is successfully reduced (i.e. to test whether participants no longer score "TENS on" trials as more painful than "TENS off" trials).
Eligibility Criteria
You may qualify if:
- Aged 18-35 years
- Good understanding of written and spoken Dutch or English
You may not qualify if:
- Severe somatic or psychiatric morbidity (e.g., heart/lung diseases, DSM-V psychiatric disorders)
- Raynaud's disease, chronic pain complaints at present or in the past
- Current pain complaints (\> 2 on NRS)
- Current use of medication (except for birth-control pill)
- Injuries on the non-dominant hand
- Refusal/inability to remove nail polish or artificial nails for the experiment
- Pregnancy or breastfeeding
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Leiden University
Leiden, 2333AK, Netherlands
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Andrea Evers, Prof
Leiden University
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- One of the groups is an open-label group, meaning there is no masking. For the other two groups, participants are not aware of group allocation, but as verbal suggestions are given regarding the device, they are not fully masked (despite being unaware of the procedures that are used). Investigators are masked until the end of calibration, to prevent the influence of the investigator on the calibration process as much as possible. Afterwards, blinding of the investigator is not possible due to the nature of the study.
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
February 17, 2022
First Posted
March 17, 2022
Study Start
March 23, 2021
Primary Completion
April 5, 2022
Study Completion
April 5, 2022
Last Updated
August 25, 2022
Record last verified: 2022-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- SAP, ANALYTIC CODE
- Time Frame
- Data will become available immediately after study publication and will be retained for 15 years.
- Access Criteria
- Data can be shared with scientists in relevant fields for the purpose of future studies such as replication or meta-analysis (or with designated persons for monitoring purposes).
All data are collected pseudonymised; consent forms are the only sources containing personal data and will not be shared, but are monitored by the department's Data Monitor.