NCT04646460

Brief 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 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.

Trial Health

63
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for not_applicable

Timeline
24mo left

Started Dec 2026

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
not yet recruiting

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

First Submitted

Initial submission to the registry

November 13, 2020

Completed
17 days until next milestone

First Posted

Study publicly available on registry

November 30, 2020

Completed
6 years until next milestone

Study Start

First participant enrolled

December 1, 2026

Expected
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2027

1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2028

Last Updated

January 16, 2026

Status Verified

January 1, 2026

Enrollment Period

1 year

First QC Date

November 13, 2020

Last Update Submit

January 14, 2026

Conditions

Keywords

Placebo effectSocial modelingConditioningPain

Outcome Measures

Primary Outcomes (3)

  • 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."

    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."

    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.

    Immediately after pain/image stimuli

Secondary Outcomes (5)

  • Skin conductance

    Immediately after pain stimuli

  • Heart rate

    Immediately after pain stimuli

  • Whole-brain maps of intervention effects

    Immediately after pain stimuli

  • CliexaEase App ratings

    Daily for: 2 weeks before scan, 2 weeks after last scan. Weekly for 1 year after last session.

  • Interpersonal Reactivity Index

    Within two weeks before first fMRI scan

Study Arms (4)

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).

Behavioral: Observed SuccessBehavioral: 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).

Behavioral: Observed FailureBehavioral: 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).

Behavioral: Observed SuccessBehavioral: 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).

Behavioral: Observed FailureBehavioral: Experienced Success

Interventions

The participant will not receive reduced stimulus intensities after the placebo treatment, so the cream is not reinforced as effective.

Observed Failure - Experienced FailureObserved Success - Experienced Failure

The demonstrator in video gets a placebo treatment, "Levoderm" analgesic cream, which will be shown to be effective at relieving pain.

Observed Success - Experienced FailureObserved Success - Experienced Success

The demonstrator in the video gets the same placebo treatment, but shows little to no effectiveness from the placebo for relieving pain.

Observed Failure - Experienced FailureObserved Failure - Experienced Success

The participant will receive reduced stimulus intensities after the placebo cream treatment to reinforce the effectiveness of the cream.

Observed Failure - Experienced SuccessObserved Success - Experienced Success

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • 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)
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Dartmouth College

Hanover, New Hampshire, 03755, United States

Location

MeSH Terms

Conditions

Pain

Condition Hierarchy (Ancestors)

Neurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Study Officials

  • Tor D Wager, PhD

    Dartmouth College

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Diana L. Taylor Distinguished Professor

Study Record Dates

First Submitted

November 13, 2020

First Posted

November 30, 2020

Study Start (Estimated)

December 1, 2026

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2028

Last Updated

January 16, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will share

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."

Time Frame
All data will be de-identified prior to sharing. Raw data will be submitted to NDA within one year from the end of data collection or 6 months from the acceptance date of the first primary study manuscript on the full dataset (excluding methods development papers), whichever is later. Analyzed data/maps of statistical results and models accompanying each paper will be submitted to NDA/OpenFMRI when the primary study manuscript is accepted.
Access Criteria
These data would generally be made available to any qualified investigator for neuroimaging studies only including: i. Research on any brain phenomenon; ii. Neuroimaging research on non-disease traits (intelligence, behavioral traits); iii. Methods development research. The requesting investigator must provide documentation of local IRB approval. These data would not be made available to: i. Any criminal justice organization, because data may not be used for any criminal justice applications; ii. Any commercial entity, because use of the data is limited to not-for-profit organizations and data may not be used for any commercial purposes.

Locations