AzTrials
AzTrials

PainPhase 1/2NCT04851301

Neural Mechanisms of Immersive Virtual Reality in Chronic Pain

A Phase 1/2 study testing Active Virtual Reality, Naloxone and Saline in people with Pain and Virtual Reality, run by University of Maryland, Baltimore at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 88 years
Conditions the study is for
Pain, Virtual Reality, Placebo
What is being tested?
Active Virtual Reality, Naloxone and Saline
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
259 participants
Where
1 siteUnited States
Study dates
1 Nov 2021to 30 Nov 2026
Phase
Phase 1/2
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 88 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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
Show all 19Show fewer
  • 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
  • High blood pressure or symptomatic low blood pressure
  • History of fainting
  • History of angioedema
  • Failed drug test (testing for opiates, cocaine, methamphetamines, amphetamines, and THC)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Luana Colloca

    Baltimore, Maryland, 21201-1512

Other trials in United States

About this study

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.

Read the detailed description

Virtual reality (VR) has been seen as an intervention for alleviating clinical chronic (and acute) pain. An approach to pain management utilizing VR presents opportunities for reducing pain and suffering by using immersive, aesthetic, and multisensory stimulation. Investigator will analyze the behavioral and neural mechanisms of active VR against sham VR as two methods that investigate descending pain modulation. Thus, the central hypothesis is that those who respond to placebos will likely respond to active VR. If VR-induced analgesia depends upon the release of endogenous opioids.

In this project, the investigators will determine the effects of VR at the neural and clinical levels directly for TMD participants, inviting participants from an existing Colloca Lab-based cohort phenotyped for diagnosis, grade, and low/high impact pain profiles and prospective TMD participants in collaboration with Johns Hopkins University. These participants have agreed to be recontacted for further research. Investigator will determine the role of the opioid tone (AIM1). In Aim 1, the investigators will determine the role of the endogenous opioid tone for VR-induced hypoalgesia in TMD participants using VR, tonic painful stimuli, and naloxone given intranasally with established mu-opioid receptor occupancy to determine how the opioid tone shapes VR-induced hypoalgesia.

Being tested
Active Virtual Reality, sham Virtual Reality, No Intervention, Naloxone, Saline
Keywords
Naloxone, Observation, TMD volunteers, VR
Medical subject headings
Pain, Temporomandibular Joint Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Active Virtual RealityBehavioural

    Also called Active VR

    Participants will be assigned to an immersive VR environment.

  • sham Virtual RealityBehavioural

    Also called Sham VR

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

  • No InterventionOther

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

  • NaloxoneDrug

    Also called Naloxone Hydrochloride/Narcan Intranasal

    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.

  • SalineOther

    Also called Placebo, Sodium chloride

    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.

  • Natural historyOther

    Participants will not be provided Naloxone or Saline.

Study groups in NCT04851301
Study groupRoleWhat they receive
NaloxoneActive comparatorNARCAN® 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.
Receives: Behavioral: Active Virtual Reality; Behavioral: sham Virtual Reality; Other: No Intervention; Drug: Naloxone
SalineSham comparatorSaline 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.
Receives: Behavioral: Active Virtual Reality; Behavioral: sham Virtual Reality; Other: No Intervention; Other: Saline
Natural HistoryOtherNatural history group, where participants will not be given any drugs. Participants will be stratified for sex and then randomized to the Natural History group.
Receives: Behavioral: Active Virtual Reality; Behavioral: sham Virtual Reality; Other: No Intervention; Other: Natural history

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ischemic pain endurance

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

    Measured: one session lasting from 2 to 3 hours

Secondary outcomes (1)

  1. Ischemic pain rating

    Increments in experimental ischemic pain endurance will be assessed using Visual Analogue Scale (VAS) (self-reported numbers) anchored from 0=no pain to 100=maximum tolerable pain. The VAS will be used every 10 seconds during the ischemic pain endurance task

    Measured: one session lasting from 2 to 3 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Apr 2021
  2. Study start1 Nov 2021
  3. Primary completion30 Dec 2025
  4. Study completion30 Nov 2026 (estimated)

Resources

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 1/2
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
259 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04851301
Sponsor's protocol ID
HP-00095888
Status last verified
Feb 2026
First submitted
6 Apr 2021
Last updated
27 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: At this time, there is neither intent nor plan to share IPD.

Publications

  • 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.

    PubMed 30817437

  • 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.

    PubMed 32345915

  • 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.

    PubMed 30216744

  • 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.

    PubMed 9870976

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Active Virtual Reality, Naloxone and Saline in people with Pain and Virtual Reality, run by University of Maryland, Baltimore 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 3 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 27 Feb 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ischemic pain endurance (time frame: one session lasting from 2 to 3 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04851301, which also lists 4 linked publications.

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 27 Feb 2026.

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