Chronic PainPIPLENCT04762836
Pain, Learning, and Nocebo
A study testing D-cycloserine, Conditioning and Extinction in people with Chronic Pain and Pain Syndrome, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Pain, Pain Syndrome
- What is being tested?
- D-cycloserine, Conditioning and Extinction
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 53 participants
- Where
- 1 siteNetherlands
- Study dates
- 28 Feb 2021to 20 Aug 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Aged 18 - 35 years
- Good understanding of the English language
- Normal or corrected to normal vision
Who cannot join
- 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)
Show all 11Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Manipulating NMDA-dependent Learning to Alter Nocebo Effects: A Pharmacological fMRI Study on Pain
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.
Read the detailed description
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:
- The difference in BOLD response at a series of a priori ROIs between pharmacological groups during the acquisition of nocebo effects.
- 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.
- The difference in BOLD response at a series of a priori ROIs between pharmacological groups during the extinction of nocebo effects.
- 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 first trials of the extinction phase.
- The difference in BOLD response at a series of a priori ROIs between pain at baseline and nocebo-augmented pain.
- 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.
- 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.
- The moderation of the magnitude of induced nocebo effects in the first trials of the extinction phase by scores on the psychological questionnaires.
- Manipulation checks: Pain intensity responses during the acquisition phase To assess the effectiveness of the conditioning paradigm, pain ratings during acquisition will be analysed using a 2x1 mixed model ANOVA with group as a between-subjects factor (DCS, placebo), and pain intensity scores as a within-subjects, repeated measure with two levels (conditioned and unconditioned trials).
Effect of DCS on learning The Wechsler Memory Scale-Fourth Edition (WMS-IV) subtest Verbal Paired Associates will be used to assess whether DCS enhanced learning. A 2x1 mixed model ANOVA with group as the between-subjects factor and WMS-IV scores as the within-subjects repeated measure with two measurements, before administering DCS or placebo versus at two hours post-administration, before the beginning of the conditioning paradigm.
- Primary hypothesis: The magnitude of the induced nocebo effect on pain is hypothesized to be larger in the DCS group relative to the placebo group. The magnitude of the nocebo effect is measured as the difference between self-reported pain on a Numeric Rating Scale (NRS) between the first conditioned and control extinction phase trials.
- Secondary hypotheses: 2.1. The magnitude of the conditioned nocebo effects still present after extinction is measured as the change from the average nocebo effect reported in the first trials of the extinction phase (after acquisition) and the average nocebo effect reported in last trials of the extinction phase (after extinction). 2.2. DCS and placebo groups will be characterized by divergent neural activity across a set of a priori regions of interest (ROIs) during acquisition. ROI analysis of differences in BOLD responses will be performed on periaqueductal grey, (PAG), ventrolateral prefrontal cortex, (vlPFC), and dorsolateral prefrontal cortex (dlPFC), amygdala, anterior cingulate cortex (aCC), hippocampus, rostral ventromedial medulla (RVM), thalamus, insula. 2.3 Multivariate pattern analysis (i.e., machine learning methods) will be used to investigate differences in BOLD responses during the acquisition of nocebo effects and thereby classify participants into pharmacological treatment groups (1) DCS, or 2) placebo) based on neural activity in the following ROIs: PAG, vlPFC, dlPFC, aCC, RVM, amygdala, thalamus, insula. 2.4. DCS and placebo groups will be characterized by divergent BOLD responses across a set of a priori ROIs during extinction. ROI analysis for differences in BOLD responses between DCS and placebo groups will be performed on the following ROIs: PAG, vlPFC, dlPFC, aCC, RVM, amygdala, thalamus, insula. 2.5 Multivariate pattern analysis will be used to investigate differences in BOLD responses during the extinction of nocebo effects and thereby classify participants into pharmacological treatment groups (1) DCS, or 2) placebo) based on neural activity in the following ROIs: PAG, vlPFC, dlPFC, aCC, RVM, amygdala, thalamus, insula. 2.6. Pain and baseline, and nocebo augmented pain of a similar intensity will be characterized by divergent neural activations. Within the placebo group, ROI analysis for differences in BOLD responses between nocebo experiences and sensory experiences of pain based on BOLD responses in the following ROIs: PAG, vlPFC, dlPFC, aCC, RVM, amygdala, thalamus, insula. 2.7. Pain and baseline, and nocebo augmented pain of a similar intensity will be characterized by divergent neural activations. Within the placebo group, multivariate pattern analysis will be used to investigate the differences in BOLD responses between nocebo experiences and sensory experiences of pain based on neural activity in the following ROIs: PAG, vlPFC, dlPFC, aCC, RVM, amygdala, thalamus, insula. . 2.8. Patterns of BOLD responses measured during the acquisition of nocebo effects in all pharmacological groups (1) DCS, or 2) placebo) at the previously listed ROIs, will predict the magnitude of nocebo effects on pain during extinction.
- Questionnaires To assess the influence of psychological traits, questionnaires will also be included. These will include the Pain Catastrophizing Scale (PSC), Spielberger State Trait Anxiety Inventory (STAI), and the Body Vigilance Scale (BVS).
- Conditions
- Chronic Pain, Pain Syndrome
- Being tested
- D-cycloserine, Conditioning, Extinction, fMRI, Placebo
- Keywords
- Nocebo, Pain, BOLD, fMRI, Conditioning
- Medical subject headings
- Chronic Pain, Somatoform Disorders, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-cycloserineDrug
Also called DCS
Antibiotic medication that augments the function of NMDA-receptors
ConditioningBehavioural
During nocebo acquisition trials, the conditioned stimulus (i.e., activation of a sham electrode that can increase pain sensitivity, is paired to unconditioned high-pain stimuli (nocebo trials). During control trials of the acquisition phase, moderate-pain stimuli are paired to no sham electrode activation.
ExtinctionBehavioural
During nocebo extinction, moderate pain stimulations are administered both after the administration of the conditioned stimulus (i.e., activation of the sham electrode) and the control stimulus (no activation of the sham electrode), in order to evoke nocebo responses to the sham hyperalgesic procedure.
fMRIOther
In both arms of the study, BOLD response data will be collected with fMRI during the acquisition and extinction of nocebo effects on pain.
PlaceboDrug
Placebo control in oral form
| Study group | Role | What they receive |
|---|---|---|
| Augmented learning | Experimental | 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 Receives: Drug: D-cycloserine; Behavioral: Conditioning; Behavioral: Extinction; Other: fMRI |
| Baseline learning | Placebo comparator | 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 Receives: Behavioral: Conditioning; Behavioral: Extinction; Other: fMRI; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Magnitude of induced nocebo hyperalgesia
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
Measured: Through study completion, an average of 2 weeks
Secondary outcomes (7)
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.
This will be measured via functional Magnetic Resonance Imaging assessing BOLD activations, for example hypo- and hyper- activation differences between the two pharmacological groups
Measured: 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.
This will be measured via functional Magnetic Resonance Imaging assessing BOLD activations, for example hypo and hyper activation differences between the two pharmacological groups
Measured: 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.
This will be measured via functional Magnetic Resonance Imaging assessing BOLD activations, for example hypo and hyper activation differences between the two pharmacological groups
Measured: 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.
This will be measured via functional Magnetic Resonance Imaging assessing BOLD activations, for example hypo and hyper activation differences between the two pharmacological groups
Measured: 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.
This will be measured via functional Magnetic Resonance Imaging assessing BOLD activations, for example hypo and hyper activation differences between the two pharmacological groups
Measured: 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.
This will be measured via functional Magnetic Resonance Imaging assessing BOLD activations, for example hypo and hyper activation differences between the two pharmacological groups
Measured: 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.
This will be measured via functional Magnetic Resonance Imaging assessing BOLD activations, for example hypo and hyper activation differences between the two pharmacological groups
Measured: Through study completion, an average of 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start28 Feb 2021
- Primary completion20 Aug 2021
- Study completion20 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Leiden University
- Responsible party
- Principal investigator, AWMEvers, Leiden University Medical Center
- Investigators
- Andrea WM Evers, PhD, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04762836
- Sponsor's protocol ID
- NL66693.058.18
- Acronym
- PIPLE
- Status last verified
- Jan 2022
- First submitted
- 13 Dec 2020
- Last updated
- 11 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All data are collected pseudonymised thus no personal data are stored or shared. Consent forms are the only sources containing personal data and will not be shared, but are monitored by the department's Data Monitor. Supporting Information: Study Protocol; Statistical Analysis Plan (SAP); Analytic Code
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Manipulating NMDA-dependent Learning to Alter Nocebo Effects: A Pharmacological fMRI Study on Pain
- ClinicalTrials.gov ID
- NCT04762836
- Acronym / sponsor ID
- PIPLE / NL66693.058.18
- Conditions
- Chronic Pain, Pain Syndrome
- Keywords
- Nocebo, Pain, BOLD, fMRI, Conditioning
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Leiden University
- Study start
- 28 Feb 2021 (actual)
- Primary completion
- 20 Aug 2021 (actual)
- Study completion
- 20 Aug 2021 (actual)
- First posted
- 21 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- The difference in BOLD response at a series of a priori ROIs between pharmacological groups during the acquisition of nocebo effects.
- 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.
- The difference in BOLD response at a series of a priori ROIs between pharmacological groups during the extinction of nocebo effects.
- 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 first trials of the extinction phase.
- The difference in BOLD response at a series of a priori ROIs between pain at baseline and nocebo-augmented pain.
- 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.
- 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.
- The moderation of the magnitude of induced nocebo effects in the first trials of the extinction phase by scores on the psychological questionnaires.
- Manipulation checks: Pain intensity responses during the acquisition phase To assess the effectiveness of the conditioning paradigm, pain ratings during acquisition will be analysed using a 2x1 mixed model ANOVA with group as a between-subjects factor (DCS, placebo), and pain intensity scores as a within-subjects, repeated measure with two levels (conditioned and unconditioned trials).
Effect of DCS on learning The Wechsler Memory Scale-Fourth Edition (WMS-IV) subtest Verbal Paired Associates will be used to assess whether DCS enhanced learning. A 2x1 mixed model ANOVA with group as the between-subjects factor and WMS-IV scores as the within-subjects repeated measure with two measurements, before administering DCS or placebo versus at two hours post-administration, before the beginning of the conditioning paradigm.
- Primary hypothesis: The magnitude of the induced nocebo effect on pain is hypothesized to be larger in the DCS group relative to the placebo group. The magnitude of the nocebo effect is measured as the difference between self-reported pain on a Numeric Rating Scale (NRS) between the first conditioned and control extinction phase trials.
- Secondary hypotheses: 2.1. The magnitude of the conditioned nocebo effects still present after extinction is measured as the change from the average nocebo effect reported in the first trials of the extinction phase (after acquisition) and the average nocebo effect reported in last trials of the extinction phase (after extinction). 2.2. DCS and placebo groups will be characterized by divergent neural activity across a set of a priori regions of interest (ROIs) during acquisition. ROI analysis of differences in BOLD responses will be performed on periaqueductal grey, (PAG), ventrolateral prefrontal cortex, (vlPFC), and dorsolateral prefrontal cortex (dlPFC), amygdala, anterior cingulate cortex (aCC), hippocampus, rostral ventromedial medulla (RVM), thalamus, insula. 2.3 Multivariate pattern analysis (i.e., machine learning methods) will be used to investigate differences in BOLD responses during the acquisition of nocebo effects and thereby classify participants into pharmacological treatment groups (1) DCS, or 2) placebo) based on neural activity in the following ROIs: PAG, vlPFC, dlPFC, aCC, RVM, amygdala, thalamus, insula. 2.4. DCS and placebo groups will be characterized by divergent BOLD responses across a set of a priori ROIs during extinction. ROI analysis for differences in BOLD responses between DCS and placebo groups will be performed on the following ROIs: PAG, vlPFC, dlPFC, aCC, RVM, amygdala, thalamus, insula. 2.5 Multivariate pattern analysis will be used to investigate differences in BOLD responses during the extinction of nocebo effects and thereby classify participants into pharmacological treatment groups (1) DCS, or 2) placebo) based on neural activity in the following ROIs: PAG, vlPFC, dlPFC, aCC, RVM, amygdala, thalamus, insula. 2.6. Pain and baseline, and nocebo augmented pain of a similar intensity will be characterized by divergent neural activations. Within the placebo group, ROI analysis for differences in BOLD responses between nocebo experiences and sensory experiences of pain based on BOLD responses in the following ROIs: PAG, vlPFC, dlPFC, aCC, RVM, amygdala, thalamus, insula. 2.7. Pain and baseline, and nocebo augmented pain of a similar intensity will be characterized by divergent neural activations. Within the placebo group, multivariate pattern analysis will be used to investigate the differences in BOLD responses between nocebo experiences and sensory experiences of pain based on neural activity in the following ROIs: PAG, vlPFC, dlPFC, aCC, RVM, amygdala, thalamus, insula. . 2.8. Patterns of BOLD responses measured during the acquisition of nocebo effects in all pharmacological groups (1) DCS, or 2) placebo) at the previously listed ROIs, will predict the magnitude of nocebo effects on pain during extinction.
- Questionnaires To assess the influence of psychological traits, questionnaires will also be included. These will include the Pain Catastrophizing Scale (PSC), Spielberger State Trait Anxiety Inventory (STAI), and the Body Vigilance Scale (BVS).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Augmented learning | Experimental | Drug: D-cycloserine, Behavioral: Conditioning, Behavioral: Extinction, Other: fMRIConditioning 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 |
| Baseline learning | Placebo comparator | Behavioral: Conditioning, Behavioral: Extinction, Other: fMRI, Drug: PlaceboConditioning 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 |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Aged 18 - 35 years
- Good understanding of the English language
- Normal or corrected to normal vision
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D-cycloserineAlso: DCSAntibiotic medication that augments the function of NMDA-receptors | Drug | Augmented learning |
| ConditioningDuring nocebo acquisition trials, the conditioned stimulus (i.e., activation of a sham electrode that can increase pain sensitivity, is paired to unconditioned high-pain stimuli (nocebo trials). During control trials of the acquisition phase, moderate-pain stimuli are paired to no sham electrode activation. | Behavioural | Augmented learning, Baseline learning |
| ExtinctionDuring nocebo extinction, moderate pain stimulations are administered both after the administration of the conditioned stimulus (i.e., activation of the sham electrode) and the control stimulus (no activation of the sham electrode), in order to evoke nocebo responses to the sham hyperalgesic procedure. | Behavioural | Augmented learning, Baseline learning |
| fMRIIn both arms of the study, BOLD response data will be collected with fMRI during the acquisition and extinction of nocebo effects on pain. | Other | Augmented learning, Baseline learning |
| PlaceboPlacebo control in oral form | Drug | Baseline learning |
Primary outcome
Magnitude of induced nocebo hyperalgesia
Time frame: 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
7 secondary outcomes
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Through study completion, an average of 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2022.
- Individual participant dataSharing planned: Yes. All data are collected pseudonymised thus no personal data are stored or shared. Consent forms are the only sources containing personal data and will not be shared, but are monitored by the department's Data Monitor. Supporting Information: Study Protocol; Statistical Analysis Plan (SAP); Analytic Code
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea WM Evers, PhD principal investigator
Leiden University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing D-cycloserine, Conditioning and Extinction in people with Chronic Pain and Pain Syndrome, run by Leiden University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Magnitude of induced nocebo hyperalgesia (time frame: Through study completion, an average of 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2022.