Neural Mechanisms of Immersive Virtual Reality in Chronic Pain

NCT04851301 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HP-00095888
• Study Type: interventional
• Target: 259
• Locations: 1 country
• Sites: 1

Brief Summary

This project examines, in chronic pain, the mechanisms of immersive virtual reality compared to the mechanisms of placebo hypoalgesia. The potential of developing new non-pharmacological premises for low-risk interventions for pain management is high.

Conditions

Pain; Virtual Reality; Placebo; Temporomandibular Disorder

Keywords

Naloxone; Observation; TMD volunteers; VR

Outcome Measures

Primary Outcomes (1)

• Ischemic pain endurance

  Increments in experimental ischemic pain endurance will be assessed using a timer (minutes of tolerance)

  one session lasting from 2 to 3 hours

Secondary Outcomes (1)

• Ischemic pain rating

  one session lasting from 2 to 3 hours

Study Arms (3)

Naloxone

ACTIVE COMPARATOR

NARCAN® Naloxone Nasal Spray will be used to determine how the opioid tone shapes VR-induced hypoalgesia. 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.

Behavioral: Active Virtual Reality; Behavioral: sham Virtual Reality; Other: No Intervention; Drug: Naloxone

Saline

SHAM COMPARATOR

Saline group, where participants will be given saline solution (4mg) via an identical spray device. Participants will be stratified for sex and then randomized to saline arm (The dose of saline will be (0.1 mL 0.9% sodium chloride intranasally), respectively. Investigators, staff, and participants will be blinded to the treatment options.

Behavioral: Active Virtual Reality; Behavioral: sham Virtual Reality; Other: No Intervention; Other: Saline

Natural History

OTHER

Natural history group, where participants will not be given any drugs. Participants will be stratified for sex and then randomized to the Natural History group.

Behavioral: Active Virtual Reality; Behavioral: sham Virtual Reality; Other: No Intervention; Other: Natural history

Interventions

sham Virtual Reality BEHAVIORAL

Participants will be assigned to a sham VR environment without the immersive experience.

Also known as: Sham VR

Naloxone; Natural History; Saline

No Intervention OTHER

Participants will experience tonic pain tolerance tests without exposure to any environments.

Naloxone; Natural History; Saline

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: Placebo, Sodium chloride

Saline

Natural history OTHER

Participants will not be provided Naloxone or Saline.

Natural History

Active Virtual Reality BEHAVIORAL

Participants will be assigned to an immersive VR environment.

Also known as: Active VR

Naloxone; Natural History; Saline

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

Eligibility Criteria

• Age: 18 Years - 88 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age (18-88 years)
• English speaker (written and spoken)
• Temporal Mandibular Disorder (TMD) for at least 3 months

You may not qualify if:

• Present or past degenerative neuromuscular disease
• Cardiovascular, neurological diseases, pulmonary abnormalities, kidney disease, liver disease, history of cancer within past 3 years
• Cervical pain other than TMD related (e.g. stenosis, radiculopathy)
• Any personal (or family first degree) history of mania, schizophrenia, or other psychoses
• Severe psychiatric condition (e.g., schizophrenia, bipolar disorders, autism) leading to hospitalization within the last 3 years.
• Use of antidepressants, ADHD medication, non-over-the-counter painkillers, methadone, benzodiazepines, barbiturates, and/or narcotics during the past 3 months
• Lifetime alcohol/drug dependence or alcohol/drug abuse in the past 3 months
• Pregnancy or breastfeeding
• Color-blindness
• Pain in jaw or temple in last 3 months due to toothache or infection
• Any facial trauma that has occurred in the last 6 weeks
• History of severe facial trauma in the last 3 months
• Impaired or uncorrected hearing
• Conditions that would interfere with the VR mask placement (e.g. trauma, burn, infection)
• Known history of severe motion sickness

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

Luana Colloca

Baltimore, Maryland, 21201-1512, United States

Location

Related Publications (4)

• Honzel E, Murthi S, Brawn-Cinani B, Colloca G, Kier C, Varshney A, Colloca L. Virtual reality, music, and pain: developing the premise for an interdisciplinary approach to pain management. Pain. 2019 Sep;160(9):1909-1919. doi: 10.1097/j.pain.0000000000001539. No abstract available.

  PMID: 30817437 BACKGROUND

• Colloca L, Raghuraman N, Wang Y, Akintola T, Brawn-Cinani B, Colloca G, Kier C, Varshney A, Murthi S. Virtual reality: physiological and behavioral mechanisms to increase individual pain tolerance limits. Pain. 2020 Sep 1;161(9):2010-2021. doi: 10.1097/j.pain.0000000000001900.

  PMID: 32345915 BACKGROUND

• 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

• Amanzio M, Benedetti F. Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems. J Neurosci. 1999 Jan 1;19(1):484-94. doi: 10.1523/JNEUROSCI.19-01-00484.1999.

  PMID: 9870976 BACKGROUND

MeSH Terms

Conditions

Pain; Temporomandibular Joint Disorders

Interventions

Exergaming; Naloxone; Sodium Chloride

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Craniomandibular Disorders; Mandibular Diseases; Jaw Diseases; Musculoskeletal Diseases; Joint Diseases; Muscular Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; 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 1
• 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: Professor

Model Details: AIM 1: This is a double-blinded, randomized, between- and within-subjects design (3 X 3) with TMD participants randomly assigned to one of three groups. The three groups are 1. Naloxone group 2. Saline group 3. Natural history group, in which participants will not be given any drugs. Within-subjects factor: All three groups will go through the following 3 conditions:1. Active VR (theBlu); 2. Sham VR; 3. No-VR.

Study Record Dates

• First Submitted: April 6, 2021
• First Posted: April 20, 2021
• Study Start: November 1, 2021
• Primary Completion: December 30, 2025
• Study Completion (Estimated): November 30, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)