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Trial record 34 of 33784 for:    Placebo AND placebo effect

Neural Correlates of Hypoalgesia Driven by Observation

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ClinicalTrials.gov Identifier: NCT03897998
Recruitment Status : Not yet recruiting
First Posted : April 1, 2019
Last Update Posted : April 1, 2019
Sponsor:
Information provided by (Responsible Party):
Luana Colloca, University of Maryland, College Park

Brief Summary:

Placebo effects held an ambivalent place in health care for at least two centuries. On the one hand, placebos are traditionally used as controls in clinical trials to correct for biases and the placebo response is viewed as an effect to be factored out in order to isolate and accurately measure the effects of the treatment. On the other hand, there is scientific evidence that placebo effects represent fascinating psychoneurobiological events involving the contribution of distinct central nervous as well as peripheral physiological mechanisms that influence pain perception and clinical pain symptoms and substantially modulate the response to pain therapeutics. Therefore, placebo effects have shifted from being a challenge for clinical trials to a resource to trigger the reduction of pain based on endogenous mechanisms that can be activated in the brain to promote hypolagesia, self-healing, and well-being. This is relevant in acute pain settings given that chronic opioid users die within approximately 2.5 years of being prescribed their first opioid medication to treat acute pain.

The overall hypothesis is that observational learning influences neural pain modulation and cognition systems, including processes associated with mentalizing (the ability to cognitively understand mental states of others), empathy (the ability to share an emotional experience), and expectancy (the anticipation of a benefit). The objective is to determine the brain mechanisms of observationally-induced analgesia using brain mapping approaches that target changes in blood oxygenation and oscillatory activity in the brain, thus enabling investigators to draw inferences about the localization and extent of neurobiological activation underlying hypoalgesia driven by observation. Therefore, the investigators designed innovative experiments using pharmacological fMRI, EEG, and combined EEG-fMRI measurements.


Condition or disease Intervention/treatment Phase
Pain Virtual Reality Placebo Drug: Naloxone Other: Saline Phase 2

Detailed Description:

Analgesic effects can also occur without formal conditioning and direct prior experience because crucial information necessary to build up expectations of analgesia can be acquired through observation of a therapeutic benefit in others. Placebo analgesic effects following the observation of a benefit in another person are similar in magnitude to those induced by directly experiencing an analgesic benefit. These observations emphasize that contextual cues substantially modulate the individual placebo analgesic effects.

In this project, the investigators propose a compelling research agenda to explore the neural mechanisms of hypoalgesia driven by observation as a foundation for future development of novel nonpharmacological pain therapies using pharmacological functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and combined EEG/fMRI. It builds on a decade of experience in placebo research in PI Colloca's lab and with University of Maryland collaborators experienced in brain mapping and pain research. In Aim 1, the investigators will determine the role of endogenous opioids on the neural mechanisms of observationally-induced hypoalgesia by using the opioid antagonist naloxone in a functional Magnetic Resonance Imaging (fMRI) setting. In Aim 2, the investigators will identify the impact of empathy by exploring how being in the immersive environment can enhance observationally-induced analgesia. In Aim 3, the investigators will leverage the EEG/fMRI to determine the neural EEG/fMRI transient changes that could co-occur when socially-induced expectations are violated.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 182 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This will be a 2 (group: naloxone vs. saline) X 2 (condition: placebo vs. control) double-blind mixed experimental design with group as the between-subjects factor and condition as the within-subjects factor. Each participant will be randomly assigned to either the naloxone or the saline group.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: The UM Pharmacy will assign de-identified study IDs to participants and provide the study drug (Naloxone or Saline) so that participants, the person conducting the experiment, and the investigator will be blind to the participant's group.
Primary Purpose: Basic Science
Official Title: Neural Correlates of Hypoalgesia Driven by Observation
Estimated Study Start Date : July 31, 2019
Estimated Primary Completion Date : July 30, 2023
Estimated Study Completion Date : July 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Naloxone
Naloxone will be used to block placebo effects during the fMRI experiment. Participants will be stratified for sex and then randomized to naloxone (0.15 mg/kg naloxone, initial bolus plus 0.2 mg/kg/hr during the fMRI experiment) or saline (0.9% sodium chloride), respectively. Investigators, staff, and participants will be blinded to the treatment options.
Drug: Naloxone

Intravenous Naloxone will be administered based on the participant's weight, with 0.15 mg/kg given as an initial bolus plus 0.2 mg/kg/hr during the fMRI experiment.

A random allocation sequence will be independently generated by the UM Pharmacy. The Principal investigator will call for each experiment.

Other Name: Naloxone Hydrochloride/Narcan Intravenous

Sham Comparator: Saline
Saline will be used as a sham comparator for blocking placebo effects during the fMRI experiment. Participants will be stratified for sex and then randomized to naloxone (0.15 mg/kg naloxone, initial bolus plus 0.2 mg/kg/hr during the fMRI experiment) or saline (0.9% sodium chloride) respectively. Investigators, staff, and participants will be blinded to the treatment options.
Other: Saline

Intravenous Normal Saline (0.9% sodium chloride) will be administered shortly before beginning the fMRI experiment.

A random allocation sequence will be independently generated by the UM Pharmacy. The Principal investigator will call for each experiment.

Other Name: Sodium chloride




Primary Outcome Measures :
  1. Neural responses [ Time Frame: Two days ]
    Blood oxygenation level dependent (BOLD) responses will allow the identification of relative activation/deactivation in the brain as result of events (e.g. painful stimulations) that will be given during the experiment and the treatment administration.


Secondary Outcome Measures :
  1. Pain ratings [ Time Frame: Two days ]
    Participants will rate painful and non-painful stimulations on a Visual Analogue Scale raging from 0=no pain to 100= maximum unbearable pain.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age (18-55 years old)
  • English speaker (written and spoken)

Exclusion Criteria:

  • Cardiovascular, neurological diseases, pulmonary abnormalities, kidney disease, liver disease, degenerative neuromuscular disease, or history of cancer within past 3 years
  • Any history of chronic pain disorder or currently in pain
  • Severe psychiatric condition (e.g. schizophrenia, bipolar disorders, mania, autism) and /or psychiatric condition leading to treatment and/or hospitalization within the last 3 years.
  • Personal history of mania, schizophrenia, or other psychoses
  • Lifetime alcohol/drug dependence, or alcohol/drug abuse in past 3 months
  • Use of antidepressants, ADHD medication, non-over-the-counter painkillers, methadone, benzodiazepines, barbiturates, and/or narcotics during the past 3 months
  • Pregnancy or breast feeding
  • Color-blindness
  • Impaired, uncorrected hearing
  • Left handed
  • Allergies or sensitivities to creams, lotions, or food coloring
  • Any non-organic implant or any non-removable metal device (e.g., pacemaker, cochlear implants, stents, surgical clips, non-removable piercings)
  • Any prior eye injury or the potential of a foreign body in the eye (e.g., worked in metal fields)
  • Persistent functional impairment due to a head trauma
  • Fear of closed spaces
  • Any other contraindications for MRI (e.g., large tattoos on head and neck)
  • Previously participated in other "Pain Perception in the Brain" Studies in Colloca lab Failed drug test (testing for opiates, cocaine, methamphetamines, amphetamines, and THC)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03897998


Contacts
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Contact: Research Coordinator 410-706-5975 NRSCollocaLab@umaryland.edu
Contact: Nathaniel Haycock, MS nhaycock@umaryland.edu

Locations
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United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201-1512
Sponsors and Collaborators
University of Maryland, College Park
Investigators
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Principal Investigator: Luana Colloca, MD/PhD/MS University of Maryland Baltimore School of Nursing

Publications:
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Responsible Party: Luana Colloca, Associate Professor, University of Maryland, College Park
ClinicalTrials.gov Identifier: NCT03897998     History of Changes
Other Study ID Numbers: HP-00085382
First Posted: April 1, 2019    Key Record Dates
Last Update Posted: April 1, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: At this time, there is neither intent nor plan to share IPD.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Luana Colloca, University of Maryland, College Park:
Naloxone
fMRI
EEG
Observation
Healthy Volunteers

Additional relevant MeSH terms:
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Naloxone
Narcotic Antagonists
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents