PainVR TMD EEGNCT06214923
Neural Mechanisms of Immersive Virtual Reality in Chronic Pain (VR TMD EEG)
A study testing RelieVRx in people with Pain and Virtual Reality, run by University of Maryland, Baltimore at 2 sites in United States.
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?
- RelieVRx
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 2 sitesUnited States
- Study dates
- 9 Apr 2024to 30 Nov 2026
- Phase
- Interventional
- 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
- TMD Grade Chronic Pain Scale (GCPS) ≥ 0
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 (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 Antipsychotics (e.g., Risperdal, Ability and clozaril)Lifetime alcohol/drug dependence or alcohol/drug abuse in past 3 months
Show all 18Show fewer
- Pregnancy or breast feeding
- Color-blindness
- Impaired or uncorrected hearing
- Non-dominant hand
- Any facial trauma that has occurred in the last 6 weeks
- History of a severe facial trauma in the last 2-3 months
- Conditions that would interfere with the VR mask placement (e.g. trauma, burn, infection)
- Known history of severe motion sickness
- Non-removable head cover, artificial hair, certain types of braids or dreadlocks
- History of fainting
- History of angioedema
- Failed drug test (testing for opiates, cocaine, methamphetamines, and amphetamines)
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Luana Colloca
Baltimore, Maryland, 21201-1512
Luana Colloca, MD,PhD,MS, 3013648089, Colloca@umaryland.edu
- Recruiting
University of Maryland
Baltimore, Maryland, 21201-1512
Luana Colloca, MD, PhD, MS, 3013648089, colloca@umaryland.edu
Katia Matychak, MS, 4107065975, asuhr@umaryland.edu
About this study
Official title: Neural Mechanisms of Immersive Virtual Reality in Chronic Pain
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.
In this study, based on our PAF study and modulation of autonomic measurements via VR, we will determine the role of acute and 3-week VR intervention to help restore PAF oscillations to normal. PAF and autonomic measurements will be collected in TMD participants characterized by low/high-impact pain. All participants will go through Active VR, Sham VR and NH phases (3-week each) where participants will be monitored for changes in cortical excitability via PAF oscillations and clinical benefit via EMA.
- Conditions
- Pain, Virtual Reality, Placebo, Temporomandibular Disorder
- Being tested
- RelieVRx, Sham-VR, No-VR (natural history control)
- Keywords
- TMD volunteers, VR, Clinical Pain, Ecological Momentary Assessment
- 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.
RelieVRxDevice
Also called Active-VR
Participants will use RelieVRx daily for 20min/day for 3 weeks
Sham-VRDevice
Participants will use Sham-VR, consisting of video, images, and sound in a head-mounted display but lack the "sense of presence" and immersive features of Active-VR (for example, scene changes with head movement). Participants will use the Sham-VR daily for 20min/day for 3 weeks
No-VR (natural history control)Other
Participants will continue regular/usual care without any VR devices (goggles or audiovisual input)
| Study group | Role | What they receive |
|---|---|---|
| High impact TMD | Other | Other: TMD Phenotype
TMD participants will be clinically phenotyped into two between-subject groups based on their score on the Graded Chronic Pain Scale (GCPS). This group will have a GCPS grade 2b, 3, and 4. Receives: Device: RelieVRx; Device: Sham-VR; Other: No-VR (natural history control) |
| Low impact TMD | Other | Other: TMD Phenotype
TMD participants will be clinically phenotyped into two between-subject groups based on their score on the Graded Chronic Pain Scale (GCPS). This group will have a GCPS grade 0, 1, and 2a Receives: Device: RelieVRx; Device: Sham-VR; Other: No-VR (natural history control) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak alpha frequency (PAF)
EEG response PAF when participants are undergoing the in-person VR
Measured: We will acquire 2-10 min of baseline EEG with open eyes and 2-10 min of EEG with closed eyes. This measurement will occur at each of the four in-person visit approximately every 3 weeks.
Objective incremental Celsius changes in heat-pain tolerance
Heat pain tolerance to incremental change in temperature will be obtained using a timer (minutes of tolerance)
Measured: The heat incremental changes range from 30 sec to 2 min tolerance. This measurement will occur at each of the four in-person visit approximately every 3 weeks.
Secondary outcomes (1)
Subjective VAS (Visual Analog Scale) scores for mood, situational anxiety, and pain intensity/unpleasantness
Participants will take Ecological Momentary Assessment questionnaires. Minimum Value: 0 Maximum Value: 100 Score interpretation: 0=not at all, 100=most/strongest For example, anxiety on a scale of 0-100, 0=no anxiety, 100=the most anxious
Measured: Daily during the 3-week condition timeframe
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2024
- Study start9 Apr 2024
- Primary completion30 May 2026
- Study completion30 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This is a 2 (high- vs. low-impact pain) by 3 (3-week Active VR vs. 3-week Sham VR vs. 3-week NH) conditions mixed experimental design. TMD participants will be clinically phenotype into high-impact or low-impact pain groups according to Graded Chronic Pain Scale (GCPS). All participants will go through Active VR, Sham VR and NH phases (3-week each). There will be 4 in-person visits where participants will be monitored for changes in cortical excitability via PAF oscillations and clinical benefit via Ecological Momentary Assessments (EMA) during the 3-week conditions. Crossover Study Model was chosen because each participant will receive VR, Sham-VR, and No-VR in random order
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Luana Colloca, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06214923
- Sponsor's protocol ID
- HP-00095888 (VR TMD EEG)
- Acronym
- VR TMD EEG
- Status last verified
- Jul 2026
- First submitted
- 18 Dec 2023
- Last updated
- 7 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- 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 30817437Colloca 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 32345915Amanzio 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 9870976Colloca 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
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neural Mechanisms of Immersive Virtual Reality in Chronic Pain
- ClinicalTrials.gov ID
- NCT06214923
- Acronym / sponsor ID
- VR TMD EEG / HP-00095888 (VR TMD EEG)
- Conditions
- Pain, Virtual Reality, Placebo, Temporomandibular Disorder
- Keywords
- TMD volunteers, VR, Clinical Pain, Ecological Momentary Assessment
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- 9 Apr 2024 (actual)
- Primary completion
- 30 May 2026 (actual)
- Study completion
- 30 Nov 2026 (estimated)
- First posted
- 22 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
In this study, based on our PAF study and modulation of autonomic measurements via VR, we will determine the role of acute and 3-week VR intervention to help restore PAF oscillations to normal. PAF and autonomic measurements will be collected in TMD participants characterized by low/high-impact pain. All participants will go through Active VR, Sham VR and NH phases (3-week each) where participants will be monitored for changes in cortical excitability via PAF oscillations and clinical benefit via EMA.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- This is a 2 (high- vs. low-impact pain) by 3 (3-week Active VR vs. 3-week Sham VR vs. 3-week NH) conditions mixed experimental design. TMD participants will be clinically phenotype into high-impact or low-impact pain groups according to Graded Chronic Pain Scale (GCPS). All participants will go through Active VR, Sham VR and NH phases (3-week each). There will be 4 in-person visits where participants will be monitored for changes in cortical excitability via PAF oscillations and clinical benefit via Ecological Momentary Assessments (EMA) during the 3-week conditions. Crossover Study Model was chosen because each participant will receive VR, Sham-VR, and No-VR in random order
| Arm | Type | Receives |
|---|---|---|
| High impact TMD | Other | Device: RelieVRx, Device: Sham-VR, Other: No-VR (natural history control)Other: TMD Phenotype TMD participants will be clinically phenotyped into two between-subject groups based on their score on the Graded Chronic Pain Scale (GCPS). This group will have a GCPS grade 2b, 3, and 4. |
| Low impact TMD | Other | Device: RelieVRx, Device: Sham-VR, Other: No-VR (natural history control)Other: TMD Phenotype TMD participants will be clinically phenotyped into two between-subject groups based on their score on the Graded Chronic Pain Scale (GCPS). This group will have a GCPS grade 0, 1, and 2a |
Who may qualify
- Ages
- 18 to 88 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age (18-88 years)
- English speaker (written and spoken)
- Temporal Mandibular Disorder (TMD) for at least 3 months
- TMD Grade Chronic Pain Scale (GCPS) ≥ 0
Key exclusion criteria (18 listed)
- Present or past degenerative neuromuscular disease
- Cardiovascular, neurological diseases, pulmonary abnormalities, kidney disease, liver disease, history of cancer within past 3 years
- Cervical pain (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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RelieVRxAlso: Active-VRParticipants will use RelieVRx daily for 20min/day for 3 weeks | Device | High impact TMD, Low impact TMD |
| Sham-VRParticipants will use Sham-VR, consisting of video, images, and sound in a head-mounted display but lack the "sense of presence" and immersive features of Active-VR (for example, scene changes with head movement). Participants will use the Sham-VR daily for 20min/day for 3 weeks | Device | High impact TMD, Low impact TMD |
| No-VR (natural history control)Participants will continue regular/usual care without any VR devices (goggles or audiovisual input) | Other | High impact TMD, Low impact TMD |
Primary outcome
Peak alpha frequency (PAF)
Time frame: We will acquire 2-10 min of baseline EEG with open eyes and 2-10 min of EEG with closed eyes. This measurement will occur at each of the four in-person visit approximately every 3 weeks.
EEG response PAF when participants are undergoing the in-person VR
Objective incremental Celsius changes in heat-pain tolerance
Time frame: The heat incremental changes range from 30 sec to 2 min tolerance. This measurement will occur at each of the four in-person visit approximately every 3 weeks.
Heat pain tolerance to incremental change in temperature will be obtained using a timer (minutes of tolerance)
1 secondary outcome
Subjective VAS (Visual Analog Scale) scores for mood, situational anxiety, and pain intensity/unpleasantness
Time frame: Daily during the 3-week condition timeframe
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2026.
- Background: PubMed 30817437Honzel 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.
- Background: PubMed 32345915Colloca 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.
- Background: PubMed 9870976Amanzio 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.
- Background: PubMed 30216744Colloca 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.
- Individual participant dataSharing planned: No. At this time, there is neither intent nor plan to share IPD.
Related trials for Pain
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Recruiting
Empowered Relief® for Cancer Survivors With Chronic Pain
Chronic Pain Due to Cancer, Pain Catastrophizing
RecruitingPhase 4
ESP Blocks for Posterior Spinal Fusion
Postoperative Pain
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruiting
Effects of Hip Hinge Exercises on Pain, Range of Motion and Functional Disability in Non-specific Low Back Pain.
Low Back Pain
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing RelieVRx in people with Pain and Virtual Reality, run by University of Maryland, Baltimore at 2 sites 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 4 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Contact Research Coordinator (410-706-5975, NRSCollocaLab@umaryland.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak alpha frequency (PAF) (time frame: We will acquire 2-10 min of baseline EEG with open eyes and 2-10 min of EEG with closed eyes. This measurement will occur at each of the four in-person visit approximately every 3 weeks.). The study lists 2 primary outcomes in all. 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 NCT06214923, 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 7 Jul 2026.