Neural Correlates of Hypoalgesia Driven by Observation

NCT03897998 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: HP-00085382
• Study Type: interventional
• Target: 211
• Locations: 1 country
• Sites: 1

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.

Conditions

Pain; Virtual Reality; Placebo

Keywords

Naloxone; fMRI; EEG; Observation; Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Neural responses

  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.

  Two days

Secondary Outcomes (1)

• Pain ratings

  Two days

Study Arms (2)

Naloxone

ACTIVE COMPARATOR

NARCAN® Naloxone Nasal Spray will be used to block placebo effects during the fMRI experiment. Participants will be stratified for sex and then randomized to naloxone (The dose of naloxone will be 4 mg, so 0.1 mL of 40 mg/ml naloxone solution given intranasally) or saline (0.1 mL 0.9% sodium chloride intranasally), respectively. Investigators, staff, and participants will be blinded to the treatment options.

Drug: Naloxone

Saline

SHAM COMPARATOR

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 (The dose of naloxone will be 4 mg, so 0.1 mL of 40 mg/ml naloxone solution given intranasally) or saline (0.1 mL 0.9% sodium chloride intranasally), respectively. Investigators, staff, and participants will be blinded to the treatment options.

Other: Saline

Interventions

Naloxone DRUG

4mg of Naloxone will be administered (0.1 mL of 40 mg/ml naloxone solution given intranasally). A random allocation sequence will be independently generated by the UM Pharmacy. The Principal investigator will call for each experiment.

Also known as: Naloxone Hydrochloride/Narcan Intranasal

Naloxone

Saline OTHER

Intranasal Normal Saline (0.1 mL 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.

Also known as: Sodium chloride

Saline

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age (18-65 years old)
• English speaker (written and spoken)

You may not qualify if:

• 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
• Nasal Polyps
• Chronic intranasal drug use ( e.g., intranasal decongestants; antihistamines)
• 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)

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland

Baltimore, Maryland, 21201-1512, United States

Location

Related Publications (3)

• Colloca L. The Placebo Effect in Pain Therapies. Annu Rev Pharmacol Toxicol. 2019 Jan 6;59:191-211. doi: 10.1146/annurev-pharmtox-010818-021542. Epub 2018 Sep 14.

  PMID: 30216744 BACKGROUND

• Schenk LA, Krimmel SR, Colloca L. Observe to get pain relief: current evidence and potential mechanisms of socially learned pain modulation. Pain. 2017 Nov;158(11):2077-2081. doi: 10.1097/j.pain.0000000000000943. No abstract available.

  PMID: 29035916 BACKGROUND

• Benedetti F, Pollo A, Colloca L. Opioid-mediated placebo responses boost pain endurance and physical performance: is it doping in sport competitions? J Neurosci. 2007 Oct 31;27(44):11934-9. doi: 10.1523/JNEUROSCI.3330-07.2007.

  PMID: 17978033 BACKGROUND

MeSH Terms

Conditions

Pain

Interventions

Naloxone; Sodium Chloride

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Luana Colloca, MD/PhD/MS

  University of Maryland Baltimore School of Nursing

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: March 29, 2019
• First Posted: April 1, 2019
• Study Start: November 1, 2021
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)