Placebo EffectNCT04646460
Context Interventions: Social Modeling and Initial Treatment Experience
A study testing Observed Success, Observed Failure and Experienced Success in people with Placebo Effect and Pain, run by Trustees of Dartmouth College at 1 site in United States.
Trial summary
In this experiment, the investigators study the brain pathways underlying several promising context interventions that enhance the strength of placebo effects. Specifically, the investigators examine the separate and joint effects of two of the most powerful context interventions: Social modeling-observing someone… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Placebo Effect, Pain
- What is being tested?
- Observed Success, Observed Failure and Experienced Success
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2026to 1 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- No current psychiatric or major neurological diagnosis
- No reported substance abuse within the last six months
- Capable of performing experimental tasks (e.g., are able to read, able to cooperate with fMRI examination)
- Fluent or native speakers of English
- No current or recent history of pathological pain or reported neurological disorders
- Abstained from alcohol and substance use for 48 hours
- Provided informed consent
- Passed fMRI screening test
Who cannot join
- Current presence of pain
- Current or past history of primary psychiatric disorder
- Current or past history of psychoactive substance abuse or dependence
- Dementias
- Movement disorders except familial tremor
- CNS infection
Show all 28Show fewer
- CNS vasculitis, inflammatory disease or autoimmune disease
- CNS demyelinating disease (e.g. multiple sclerosis)
- Space occupying lesions (mass lesions, tumors)
- Congenital CNS abnormality (e.g. cerebral palsy)
- Seizure disorder
- History of closed head trauma with loss of consciousness
- History of cerebrovascular disease (stroke, TIAs)
- Abnormal MRI (except changes accounted for by technical factors or UBOs)
- Neuroendocrine disorders (e.g., Cushings disease)
- Uncorrected hypothyroidism or hyperthyroidism
- Current or past history of cancer
- Recent history (within two years) of myocardial infarction, severe cardiovascular disease, or currently active cardiovascular disease (e.g. angina, cardiomyopathy)
- Uncontrolled hypertension or hypotension
- Chronic pain syndromes
- Chronic fatigue syndromes
- Subjects unable to tolerate the scanning procedures (e.g., claustrophobia)
- Prior treatment within the last month with any of the following: antidepressants, mood stabilizers, glucocorticoids, opiates
- Prior treatment with any of the following: antipsychotics, isoniazid, centrally active antihypertensive drugs (e.g. clonidine, reserpine)
- Metal in body or prior history working with metal fragments (e.g., as a machinist)
- Pregnancy
- Any other contraindications for MRI examination (e.g., metallic implants such as pacemakers, surgical aneurysm clips, or known metal fragments embedded in the body)
- Claustrophobia
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Dartmouth College
Hanover, New Hampshire, 03755
Bethany Hunt, BA, bethany.j.hunt@dartmouth.edu
About this study
In this experiment, the investigators study the brain pathways underlying several promising context interventions that enhance the strength of placebo effects. Specifically, the investigators examine the separate and joint effects of two of the most powerful context interventions: Social modeling-observing someone else being effectively treated-and prior treatment success or failure experiences. Participants will be randomized into 4 groups (Social modeling: observed success vs. observed failure and Conditioning: experienced success vs. experienced failure). The objectives are to investigate the placebo effect on pain relief and aversive image stimuli between and within-subjects. Each group will undergo a behavioral induction phase, fMRI placebo test phase, and an identical 3-month follow up fMRI placebo test phase. Follow-up assessment will provide some of the first evidence on predictors of the durability of placebo and context interventions.
Read the detailed description
Background:
Humans are highly social creatures, and others' behavior and experiences can have profound effects on symptoms, physiology, and behavior. Social modeling-watching a similar other experience treatment benefits-may also strongly enhance placebo effects and their durability over time, particularly when combined with other context interventions. Social influences can affect core motivational circuitry (e.g., nAC and amygdala), shape learning trajectories, and appears to have distinct mechanisms from other (e.g., conditioning) manipulations. Their impact on brain mechanisms of placebo has not been studied. Likewise, initial perceived treatment success or failure can powerfully shape learning trajectories and placebo analgesia. Initial failure experiences with a treatment type (e.g., pill) may explain some of the treatment failures in studies that (a) attempt to wash out placebo responses with ineffective pills before starting verum drug, or (b) re-randomize non-responders to different pills, as in the STAR*D antidepressant study. But the effects of initial success/failure experiences on the brain mechanisms of placebo effects have not been studied.
Design:
In an initial observation phase, participants will watch a video of another participant ("demonstrator") undergoing the baseline assessment and placebo test procedure. Next, participants will undergo a conditioning phase. The intervention is a 2 x 2 factorial between-groups manipulation (N = 30 per group) of social modeling (Observed treatment success vs. failure) and participants' initial success experience (Experienced success vs. failure). Thus, the demonstrator will either show strong signs of pain relief during placebo (Observed-Success condition) or no signs of relief (Observed-Failed treatment). During the conditioning phase, all participants will experience high-intensity heat before placebo treatment and then either low-intensity heat after application of a placebo cream, as in the investigator's and others' past work, creating experience of pain relief (Experienced-Success condition) or they will not experience relief (i.e., temperatures will not be lowered; Experienced-Failed treatment). In a subsequent fMRI test phase, participants experience painful heat and aversive IAPS images (as a transfer/specificity test) during fMRI, on skin sites treated with Control and Placebo creams, in a Control -> Placebo -> Control block design as in past research. Finally, a 3-month follow-up fMRI test phase, without additional observation or conditioning, will assess durability of brain and behavioral placebo effects.
- Conditions
- Placebo Effect, Pain
- Being tested
- Observed Success, Observed Failure, Experienced Success, Experienced Failure
- Keywords
- Placebo effect, Social modeling, Conditioning, Pain
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Observed SuccessBehavioural
The demonstrator in video gets a placebo treatment, "Levoderm" analgesic cream, which will be shown to be effective at relieving pain.
Observed FailureBehavioural
The demonstrator in the video gets the same placebo treatment, but shows little to no effectiveness from the placebo for relieving pain.
Experienced SuccessBehavioural
The participant will receive reduced stimulus intensities after the placebo cream treatment to reinforce the effectiveness of the cream.
Experienced FailureBehavioural
The participant will not receive reduced stimulus intensities after the placebo treatment, so the cream is not reinforced as effective.
| Study group | Role | What they receive |
|---|---|---|
| Observed Success - Experienced Success | Experimental | This participant group (N=30) will witness a successful placebo during the "observation phase" (i.e. the demonstrator will display reduced pain expressions after receiving the cream) and experience a successful placebo during the "experience phase" (i.e. the experimenter will reduce the intensity of the pain stimuli after applying the cream). Receives: Behavioral: Observed Success; Behavioral: Experienced Success |
| Observed Failure - Experienced Failure | Experimental | This participant group (N=30) will witness a failed placebo during the "observation phase" (i.e. the demonstrator will not display reduced pain expressions after receiving the cream) and experience a failed placebo during the "experience phase" (i.e. the experimenter will not reduce the intensity of the pain stimuli after applying the cream). Receives: Behavioral: Observed Failure; Behavioral: Experienced Failure |
| Observed Success - Experienced Failure | Experimental | This participant group (N=30) will witness a successful placebo during the "observation phase" (i.e. the demonstrator will not display reduced pain expressions after receiving the cream) and experience a failed placebo during the "experience phase" (i.e. the experimenter will not reduce the intensity of the pain stimuli after applying the cream). Receives: Behavioral: Observed Success; Behavioral: Experienced Failure |
| Observed Failure - Experienced Success | Experimental | This participant group (N=30) will witness a successful placebo during the "observation phase" (i.e. the demonstrator will display reduced pain expressions after receiving the cream) and experience a successful placebo during the "experience phase" (i.e. the experimenter will reduce the intensity of the pain stimuli after applying the cream). Receives: Behavioral: Observed Failure; Behavioral: Experienced Success |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intervention effects on pain ratings
Pain ratings will be given on a 0-100 scale. 0 being "no pain at all" and 100 being "most pain imaginable in the context of this study."
Measured: Immediately after pain stimuli
Intervention effects on aversive image ratings
Aversive ratings will be given on a 0-100 scale. 0 being "not unpleasant at all" and 100 being "very unpleasant."
Measured: Immediately after aversive image stimuli
Brain: signature responses to pain and aversive images
A priori regions of interest response from the brain (fMRI) patterns to the pain and aversive images.
Measured: Immediately after pain/image stimuli
Secondary outcomes (5)
Skin conductance
Skin conductance response (SCR) will be recorded during the task.
Measured: Immediately after pain stimuli
Heart rate
Heart rate will be recorded during the task.
Measured: Immediately after pain stimuli
Whole-brain maps of intervention effects
Exploratory brain analysis will include univariate voxel-wise maps comparing participant groups with a threshold of q < 0.05, False Discovery Rate (FDR)-corrected.
Measured: Immediately after pain stimuli
CliexaEase App ratings
Participants click an "I feel" button to display a list of feelings (i.e., happiness, sadness, pain, fear, stress, etc.), and then can drag a feeling bubble to a bodily location (or to a location indicating "not felt in the body"), and then rate the intensity of the feeling on a visual analog scale. This assessment is open-ended to minimize demand characteristics.
Measured: Daily for: 2 weeks before scan, 2 weeks after last scan. Weekly for 1 year after last session.
Interpersonal Reactivity Index
A rating of dispositional empathy with responses answered on a 5-point Likert scale ranging from "does not describe me well" to "describes me very well." Higher scores indicate more empathetic responses.
Measured: Within two weeks before first fMRI scan
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2020
- Study start1 Dec 2026 (estimated)
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Placebo EffectStudies 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
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Trustees of Dartmouth College
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tor Wager, Trustees of Dartmouth College
- Investigators
- Tor D Wager, PhD, Principal investigator, Dartmouth College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04646460
- Sponsor's protocol ID
- 230137
- Status last verified
- Jan 2026
- First submitted
- 13 Nov 2020
- Last updated
- 16 Jan 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The investigators are strongly committed to contributing to open and reproducible science. All MRI and behavioral data will be submitted to the NIMH Data Archive (NDA) according to the terms and conditions outlined on their website (https://ndar.nih.gov/contribute\_data\_sharing\_regimen.html ) and with OpenFMRI. The investigators will ensure that our IRB has approved our Data Sharing Plan. The investigators will use an informed consent document that permits subjects to allow sharing of de-identified (face removed) MRI and fMRI data with open-sharing repositories, including the NDA and OpenFMRI databases. The consent form will stipulate that: "Scientists can use my information, without personal identifiers, for any kind of genetic research."
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Context Interventions: Social Modeling and Initial Treatment Experience
- ClinicalTrials.gov ID
- NCT04646460
- Acronym / sponsor ID
- 230137
- Conditions
- Placebo Effect, Pain
- Keywords
- Placebo effect, Social modeling, Conditioning, Pain
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Trustees of Dartmouth CollegeUniversity, hospital or other
- Study start
- 1 Dec 2026 (estimated)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 30 Nov 2020 (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.
In this experiment, the investigators study the brain pathways underlying several promising context interventions that enhance the strength of placebo effects. Specifically, the investigators examine the separate and joint effects of two of the most powerful context interventions: Social modeling-observing someone else being effectively treated-and prior treatment success or failure experiences. Participants will be randomized into 4 groups (Social modeling: observed success vs. observed failure and Conditioning: experienced success vs. experienced failure). The objectives are to investigate the placebo effect on pain relief and aversive image stimuli between and within-subjects. Each group will undergo a behavioral induction phase, fMRI placebo test phase, and an identical 3-month follow up fMRI placebo test phase. Follow-up assessment will provide some of the first evidence on predictors of the durability of placebo and context interventions.
Detailed description
Background:
Humans are highly social creatures, and others' behavior and experiences can have profound effects on symptoms, physiology, and behavior. Social modeling-watching a similar other experience treatment benefits-may also strongly enhance placebo effects and their durability over time, particularly when combined with other context interventions. Social influences can affect core motivational circuitry (e.g., nAC and amygdala), shape learning trajectories, and appears to have distinct mechanisms from other (e.g., conditioning) manipulations. Their impact on brain mechanisms of placebo has not been studied. Likewise, initial perceived treatment success or failure can powerfully shape learning trajectories and placebo analgesia. Initial failure experiences with a treatment type (e.g., pill) may explain some of the treatment failures in studies that (a) attempt to wash out placebo responses with ineffective pills before starting verum drug, or (b) re-randomize non-responders to different pills, as in the STAR*D antidepressant study. But the effects of initial success/failure experiences on the brain mechanisms of placebo effects have not been studied.
Design:
In an initial observation phase, participants will watch a video of another participant ("demonstrator") undergoing the baseline assessment and placebo test procedure. Next, participants will undergo a conditioning phase. The intervention is a 2 x 2 factorial between-groups manipulation (N = 30 per group) of social modeling (Observed treatment success vs. failure) and participants' initial success experience (Experienced success vs. failure). Thus, the demonstrator will either show strong signs of pain relief during placebo (Observed-Success condition) or no signs of relief (Observed-Failed treatment). During the conditioning phase, all participants will experience high-intensity heat before placebo treatment and then either low-intensity heat after application of a placebo cream, as in the investigator's and others' past work, creating experience of pain relief (Experienced-Success condition) or they will not experience relief (i.e., temperatures will not be lowered; Experienced-Failed treatment). In a subsequent fMRI test phase, participants experience painful heat and aversive IAPS images (as a transfer/specificity test) during fMRI, on skin sites treated with Control and Placebo creams, in a Control -> Placebo -> Control block design as in past research. Finally, a 3-month follow-up fMRI test phase, without additional observation or conditioning, will assess durability of brain and behavioral placebo effects.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Observed Success - Experienced Success | Experimental | Behavioral: Observed Success, Behavioral: Experienced SuccessThis participant group (N=30) will witness a successful placebo during the "observation phase" (i.e. the demonstrator will display reduced pain expressions after receiving the cream) and experience a successful placebo during the "experience phase" (i.e. the experimenter will reduce the intensity of the pain stimuli after applying the cream). |
| Observed Failure - Experienced Failure | Experimental | Behavioral: Observed Failure, Behavioral: Experienced FailureThis participant group (N=30) will witness a failed placebo during the "observation phase" (i.e. the demonstrator will not display reduced pain expressions after receiving the cream) and experience a failed placebo during the "experience phase" (i.e. the experimenter will not reduce the intensity of the pain stimuli after applying the cream). |
| Observed Success - Experienced Failure | Experimental | Behavioral: Observed Success, Behavioral: Experienced FailureThis participant group (N=30) will witness a successful placebo during the "observation phase" (i.e. the demonstrator will not display reduced pain expressions after receiving the cream) and experience a failed placebo during the "experience phase" (i.e. the experimenter will not reduce the intensity of the pain stimuli after applying the cream). |
| Observed Failure - Experienced Success | Experimental | Behavioral: Observed Failure, Behavioral: Experienced SuccessThis participant group (N=30) will witness a successful placebo during the "observation phase" (i.e. the demonstrator will display reduced pain expressions after receiving the cream) and experience a successful placebo during the "experience phase" (i.e. the experimenter will reduce the intensity of the pain stimuli after applying the cream). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- No current psychiatric or major neurological diagnosis
- No reported substance abuse within the last six months
- Capable of performing experimental tasks (e.g., are able to read, able to cooperate with fMRI examination)
- Fluent or native speakers of English
- No current or recent history of pathological pain or reported neurological disorders
Key exclusion criteria (28 listed)
- Current presence of pain
- Current or past history of primary psychiatric disorder
- Current or past history of psychoactive substance abuse or dependence
- Dementias
- Movement disorders except familial tremor
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 |
|---|---|---|
| Observed SuccessThe demonstrator in video gets a placebo treatment, "Levoderm" analgesic cream, which will be shown to be effective at relieving pain. | Behavioural | Observed Success - Experienced Failure, Observed Success - Experienced Success |
| Observed FailureThe demonstrator in the video gets the same placebo treatment, but shows little to no effectiveness from the placebo for relieving pain. | Behavioural | Observed Failure - Experienced Failure, Observed Failure - Experienced Success |
| Experienced SuccessThe participant will receive reduced stimulus intensities after the placebo cream treatment to reinforce the effectiveness of the cream. | Behavioural | Observed Failure - Experienced Success, Observed Success - Experienced Success |
| Experienced FailureThe participant will not receive reduced stimulus intensities after the placebo treatment, so the cream is not reinforced as effective. | Behavioural | Observed Failure - Experienced Failure, Observed Success - Experienced Failure |
Primary outcome
Intervention effects on pain ratings
Time frame: Immediately after pain stimuli
Pain ratings will be given on a 0-100 scale. 0 being "no pain at all" and 100 being "most pain imaginable in the context of this study."
Intervention effects on aversive image ratings
Time frame: Immediately after aversive image stimuli
Aversive ratings will be given on a 0-100 scale. 0 being "not unpleasant at all" and 100 being "very unpleasant."
Brain: signature responses to pain and aversive images
Time frame: Immediately after pain/image stimuli
A priori regions of interest response from the brain (fMRI) patterns to the pain and aversive images.
5 secondary outcomes
Skin conductance
Time frame: Immediately after pain stimuli
Heart rate
Time frame: Immediately after pain stimuli
Whole-brain maps of intervention effects
Time frame: Immediately after pain stimuli
CliexaEase App ratings
Time frame: Daily for: 2 weeks before scan, 2 weeks after last scan. Weekly for 1 year after last session.
Interpersonal Reactivity Index
Time frame: Within two weeks before first fMRI scan
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2026.
- Individual participant dataSharing planned: Yes. The investigators are strongly committed to contributing to open and reproducible science. All MRI and behavioral data will be submitted to the NIMH Data Archive (NDA) according to the terms and conditions outlined on their website (https://ndar.nih.gov/contribute_data_sharing_regimen.html ) and with OpenFMRI. The investigators will ensure that our IRB has approved our Data Sharing Plan. The investigators will use an informed consent document that permits subjects to allow sharing of de-identified (face removed) MRI and fMRI data with open-sharing repositories, including the NDA and OpenFMRI databases. The consent form will stipulate that: "Scientists can use my information, without personal identifiers, for any kind of genetic research."
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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.
Tor D Wager, PhD principal investigator
Dartmouth College
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Observed Success, Observed Failure and Experienced Success in people with Placebo Effect and Pain, run by Trustees of Dartmouth College at 1 site in United States.
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 8 inclusion and 28 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: opening soon, as of the sponsor's last update on 16 Jan 2026. 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 United States. 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. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tor D Wager, PhD (603-646-2196, Tor.D.Wager@Dartmouth.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intervention effects on pain ratings (time frame: Immediately after pain stimuli). The study lists 3 primary outcomes in all. 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 16 Jan 2026.