Virtual Reality and Cranial Nerve Neuromodulation to Manage Chronic Pain

NCT ID: NCT07065396

Last Updated: 2025-07-15

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-31
• Study Completion Date: 2026-08-31

Brief Summary

In Canada, veterans suffer from chronic pain at twice the rate of the general population. This pain is often linked to post-traumatic stress disorder (PTSD), and both have a major impact on their quality of life. The autonomic nervous system (ANS) plays a key role in these pathologies, making its modulation a promising therapeutic target. Virtual reality (VR) is already being used to alleviate pain and PTSD in veterans, mainly by modulating ANS reactivity. Two types of VR exist: prolonged exposure (desensitization) and the calming effect, the latter being better tolerated and more suitable for rebalancing the ANS. However, its effects on pain remain modest and temporary. To reinforce these benefits, it is proposed to combine VR with a new approach called cranial nerve non-invasive neuromodulation (CN-NINM), an innovative technique that allows the generation of a direct flow of neuronal impulses via the stimulation of the tongue. The goal of this project is therefore to document the efficacy of VR and the combination of VR and CN-NINM on pain and ANS in veterans suffering from chronic pain and PTSD. VR, CN-NINM and the combination of the two will be applied for 20 minutes. Clinical pain, experimental pain and ANS reactivity will be assessed before and after the interventions. At the end of this study, it is expected that the investigators will be able to document the type of effect CN-NINM could have, and that it could become a complementary therapeutic option.

Detailed Description

In Canada, many veterans suffer from chronic pain, with a prevalence twice as high as that of the general population. Chronic pain is often linked to post-traumatic stress disorder(PTSD). Together, these two conditions impact on the functioning and quality of life of veterans. Recent studies suggest that the autonomic nervous system (ANS) plays a central role in the pathophysiology of chronic pain and PTSD, making it a prime therapeutic target.

Virtual reality (VR) is already being used with veterans, and its effectiveness in relieving pain and PTSD is well documented in veterans, notably by modulating ANS reactivity. Two types of VR approaches are commonly used: VR with prolonged exposure (desensitization) and VR with a calming effect (aimed at normalizing the stress response and SNA reactivity).The latter is better tolerated than prolonged-exposure VR and remains better suited to rebalancing ANS reactivity and relieving symptoms. It calms the ANS and relieves pain (acute and chronic) when combined with traditional rehabilitation, but its effects on pain intensity remain modest and limited in time.

To optimize the benefits of VR, it is proposed to combine VR with a non-pharmacological method, as suggested by experts. This non-pharmacological approach is cranial nerve non-invasive neuromodulation (CN-NINM). CN-NINM is an innovative approach that stimulates the cranial nerves via electrodes placed directly on the tongue; the impulses reach and modulate the activity of ANS structures located in the brainstem. These structures are linked to autonomic functions and pain modulation. This combination could reinforce and prolong the positive effects of VR on veterans' pain.

Objectives: 1) To document the effect of VR (an intervention currently provided) on pain and ANS reactivity in veterans with PTSD, 2) to assess the ability of CN-NINM (vs sham CN-NINM) to potentiate the effects of VR on pain and on ANS reactivity.

Methods: In this within-subjects factorial crossover design, 15 veterans will be recruited. Sociodemographic, pain and PTSD-related variables will be collected to confirm participant eligibility. Prior to the interventions, participants will undergo an assessment of both clinical pain (intensity and unpleasantness of pain, numerical scale 0-10) and experimental pain. The tonic thermal experimental pain paradigm involves the application of a thermode (hotplate) to participants' forearms. Thermal nociceptive stimuli will be induced for 2 minutes on the participants' forearm using the thermode. Although the temperature remains constant for the entire 2 minutes, the participant will be informed that the temperature may increase, decrease, or remain stable during the procedure. The participant will then, at all times, evaluate the intensity of the pain with a visual analogue scale connected to a computer(CoVAS: visual analogue scale from 0 to 100).

Additionally, participants will complete clinical questionnaires assessing anxiety, pain and PTSD-related symptoms. Various autonomic measures (blood pressure, heart rate reactivity [HRV], electrodermal response) will also be taken to characterize ANS reactivity before and after each intervention. Participants will receive the 3 interventions (VR, VR+CN-NINM and VR+ sham CN-NINM) randomly assigned. The VR headset will broadcast calming images for 20 minutes. CN-NINM will be applied, using a portable stimulator, placed directly on the tongue of the participants for 20 minutes simultaneously with VR.

Conditions

Chronic Pain; PTSD - Post Traumatic Stress Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Virtual reality (VR)

VR interventions (hypnotic suggestions with auditory and visual calming stimulations) will applied for 20 minutes.

Group Type: EXPERIMENTAL

Virtual reality

Intervention Type: PROCEDURE

The VR intervention will take place in a quiet room. The participant will be installed in a seated position, wearing a virtual reality headset that includes an audio device playing sounds. The eyes are covered by a mask featuring a screen showing calming 3D VR images (e.g. beach landscapes), designed by our team. The intervention lasts 20 minutes. The hypnotic suggestions with auditory and visual calming stimulations will help the person to focus on the present moment, to reduce anxiety and painful sensations.

Virtual reality (VR) + Cranial nerve non-invasive neuromodulation (CN-NINM)

CN-NINM will be applied during the VR interventions (20 min).

Group Type: EXPERIMENTAL

Virtual reality

Intervention Type: PROCEDURE

The VR intervention will take place in a quiet room. The participant will be installed in a seated position, wearing a virtual reality headset that includes an audio device playing sounds. The eyes are covered by a mask featuring a screen showing calming 3D VR images (e.g. beach landscapes), designed by our team. The intervention lasts 20 minutes. The hypnotic suggestions with auditory and visual calming stimulations will help the person to focus on the present moment, to reduce anxiety and painful sensations.

Cranial nerve non-invasive neuromodulation (CN-NINM)

Intervention Type: PROCEDURE

During each intervention including CN-NINM, this latter will be applied for 20 minutes, with the help of a portable stimulator comprising a network of 18 electrodes, directly on the tongue of the participants. The participants will hold the CN-NINM in place by pressing their tongue upwards. The CN-NINM will generate high-frequency pulses (50 µsec to 150 Hz), and the intensity of the stimulus will be set by each participant to a comfortable level of sensation, similar to the sensation in the mouth of a soft drink.

Virtual reality (VR) + sham CN-NINM

Sham CN-NINM (no stimulation) will be applied during the VR interventions (20 min).

Group Type: PLACEBO_COMPARATOR

Virtual reality

Intervention Type: PROCEDURE

The VR intervention will take place in a quiet room. The participant will be installed in a seated position, wearing a virtual reality headset that includes an audio device playing sounds. The eyes are covered by a mask featuring a screen showing calming 3D VR images (e.g. beach landscapes), designed by our team. The intervention lasts 20 minutes. The hypnotic suggestions with auditory and visual calming stimulations will help the person to focus on the present moment, to reduce anxiety and painful sensations.

Placebo CN-NINM

Intervention Type: PROCEDURE

In this study, we will have a control intervention which will be placebo CN-NINM. For placebo CN-NINM, participants will wear the device such as the real CN-NINM group, without having experienced the tingling sensation beforehand, so they will not know what the CN-NINM potential effect is.

Interventions

Virtual reality

The VR intervention will take place in a quiet room. The participant will be installed in a seated position, wearing a virtual reality headset that includes an audio device playing sounds. The eyes are covered by a mask featuring a screen showing calming 3D VR images (e.g. beach landscapes), designed by our team. The intervention lasts 20 minutes. The hypnotic suggestions with auditory and visual calming stimulations will help the person to focus on the present moment, to reduce anxiety and painful sensations.

Intervention Type: PROCEDURE

Cranial nerve non-invasive neuromodulation (CN-NINM)

During each intervention including CN-NINM, this latter will be applied for 20 minutes, with the help of a portable stimulator comprising a network of 18 electrodes, directly on the tongue of the participants. The participants will hold the CN-NINM in place by pressing their tongue upwards. The CN-NINM will generate high-frequency pulses (50 µsec to 150 Hz), and the intensity of the stimulus will be set by each participant to a comfortable level of sensation, similar to the sensation in the mouth of a soft drink.

Intervention Type: PROCEDURE

Placebo CN-NINM

In this study, we will have a control intervention which will be placebo CN-NINM. For placebo CN-NINM, participants will wear the device such as the real CN-NINM group, without having experienced the tingling sensation beforehand, so they will not know what the CN-NINM potential effect is.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. Be a veteran;

2. Be ≥30 years old;

3. Have a diagnosis of chronic musculoskeletal pain (pain > 6 months);

4. Have been diagnosed with PTSD by a health professional and/or have a PTSD Checklist for DSM-5 (PCL-5) score > 30/80 and

5. Speak English or French.

Exclusion Criteria

1. Bipolar disorder, psychosis;

2. Neuropathic pain (based on the Neuropathic Pain Diagnosis and Questionnaire (DN4));

3. Visual disorders or photosensitivity, color blindness;

4. Epilepsy, motion sickness and

5. Any containdications to CN-NINM.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chronic Pain Center of Excellence for Canadian Veterans

UNKNOWN

Sponsor Role: collaborator

Quebec Pain Research Network

OTHER

Sponsor Role: collaborator

Université de Sherbrooke

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guillaume Léonard, PhD

Role: PRINCIPAL_INVESTIGATOR

Université de Sherbrooke

Locations

Centre de recherche sur le vieillissement (CdRV)

Sherbrooke, Quebec, Canada

Countries

Canada

Central Contacts

Guillaume Léonard, PhD

Role: CONTACT

guillaume.leonard2@usherbrooke.ca

819-821-8000 ext. 72933

Maureen Ahiatsi, MSc

Role: CONTACT

maureen.rudy.sandra.ahiatsi@usherbrooke.ca

819-780-2220 ext. 45691

Facility Contacts

Guillaume Léonard, PhD

Role: primary

guillaume.leonard2@usherbrooke.ca

819-821-8000 ext. 72933

Maureen Ahiatsi, MSc

Role: backup

maureen.rudy.sandra.ahiatsi@usherbrooke.ca

819-446-4220 ext. 45691

Other Identifiers

2025-5448a

Identifier Type: -

Identifier Source: org_study_id