Neuropathic PainNCT06577649
Pain and Perceptual Distortion of Face
A study testing Active repetitive transcranial magnetic stimulation (rTMS) in people with Neuropathic Pain and Orofacial Pain, run by University of Aarhus at 1 site in Denmark.
Trial summary
Post-traumatic trigeminal neuropathic pain (PTNP) is "a unilateral or bilateral facial or oral pain following and caused by trauma to the trigeminal nerve(s), with other symptoms and/or clinical signs of trigeminal nerve dysfunction, and persisting or recurring for more than 3 months". Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Neuropathic Pain, Orofacial Pain
- What is being tested?
- Active repetitive transcranial magnetic stimulation (rTMS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteDenmark
- Study dates
- 9 Sep 2022to 11 Jul 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Persistent Post-traumatic trigeminal neuropathic pain patients for 6 months or longer
- Stable on analgesic medication
Who cannot join
- past history of TMS therapy or TMS-related contraindications (pacemaker, epilepsy etc.).
- Major stroke
- Pregnancy
- Severe organic brain damage
Trial locations and contacts
1 site in 1 country.
About this study
Official title: From Pain in the Face to Perceptual Distortion: Exploring Mechanisms and Novel Treatment Strategies
Post-traumatic trigeminal neuropathic pain (PTNP) is "a unilateral or bilateral facial or oral pain following and caused by trauma to the trigeminal nerve(s), with other symptoms and/or clinical signs of trigeminal nerve dysfunction, and persisting or recurring for more than 3 months". PTNP may result from a major craniofacial/oral trauma or may be subsequent to relatively minor dental treatments such as teeth extractions, surgeries, root canal treatment. Patients suffering from this condition have a significantly reduced quality of life. Unfortunately, the currently available management modalities are associated with limited success and side effects.
Repetitive transcranial magnetic stimulation (rTMS), which is a safe, non-invasive brain stimulation technique has emerged as a potential treatment for chronic pain. In this study, the purpose is to explore the potential of rTMS in treating the persistent neuropathic pain by providing individualized treatment for the sufferers.
Read the detailed description
In addition to pain, a curious observation in people with PTNP is that they report that the painful facial area is "swollen" or "feels differently". There are often no clinical signs or physical differences present, hence such self-reported "illusions" may represent a kind of disrupted body image or a "perceptual distortion" of the face and can be speculated to contribute to the maintenance of facial pain. rTMS paradigms are being widely applied in both therapeutic and investigative studies.In this project, the aim is to employ continuous theta-burst stimulation (cTBS), an inhibitory rTMS paradigm, to evaluate its effect on pain perception and PD in people with PTNP.
In this project, people with PTNP (N=9) received a rTMS (50 Hz, 600 pulses for 40s) session/week as intervention for four consecutive weeks at the primary somatosensory cortex (face area) in a "n-of-1" single-blinded randomized controlled cross-over design: (A) active-sham-active-sham or (B) sham-active-sham-active. That is the same participant received both active and sham either in the (A) order or (B). Pain intensity and perceptual distortion (PD) as perceived size changes of the affected face area were measured at baseline, immediately, 60 mins after rTMS in each session and end of the session (a week after rTMS), one and three months after rTMS. Questionnaires on quality of life, jaw function, sleep quality were also assessed. Changes in pain and PD after each intervention were evaluated.
- Conditions
- Neuropathic Pain, Orofacial Pain
- Being tested
- Active repetitive transcranial magnetic stimulation (rTMS), Sham repetitive transcranial magnetic stimulation (sham rTMS)
- Keywords
- Repetitive transcranial magnetic stimulation, N-of-1 trials, Perceptual distortion, Post-traumatic trigeminal neuropathic pain
- Medical subject headings
- Neuralgia, Facial Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active repetitive transcranial magnetic stimulation (rTMS)Device
cTBS (50 Hz, 600 pulses, 80% resting motor threshold) for 40s was applied continuously as active rTMS at the face representation area of primary somatosensory cortex (S1)
Sham repetitive transcranial magnetic stimulation (sham rTMS)Device
A sham rTMS was applied using the same stimulation parameters as with cTBS, but using a placebo coil, which produced similar sound as the real coil.
| Study group | Role | What they receive |
|---|---|---|
| Active group | Active comparator | Continuous theta burst stimulation Receives: Device: Active repetitive transcranial magnetic stimulation (rTMS) |
| Sham group | Sham comparator | Sham repetitive transcranial magnetic stimulation (rTMS) Receives: Device: Sham repetitive transcranial magnetic stimulation (sham rTMS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in pain intensity
Changes in pain intensity from baseline to end of each session measured using self-reported pain dairy using a 0-10 visual analog scale (VAS; 0=no pain and 10=worst pain imaginable). The intervention (active and sham rTMS) were each given in 2 sessions. In total, the participant received 4 sessions of intervention.
Measured: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention).
Changes in perceptual distortion
Perceptual distortion defined as perceived change in the size/shape of the affected face area will be measured using Numerical Rating Scale ranging from -100% through 0% to +100%, where 0% = no size change, -100% = half the size and +100% = double the size in comparison with non-affected side of face and drawings of the affected area. The changes will be measured from baseline to the end of each session as done for pain intensity.
Measured: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention).
Secondary outcomes (8)
Changes in sleep quality
Measured using the Pittsburgh Sleep Quality Index (PSQI-DK). Seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality.
Measured: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Changes in perceived health or health related quality of life
Will be measured using Short Form Survey-36- (SF -36).The instrument includes scales for physical functioning, social functioning, role limitations due to physical or emotional problems, mental health, energy, pain and general health perception. It consists of 36 items. Each item is graded on a scale of 0 to 100, with 0 and 100 serving as the lowest and highest possible scores respectively. A high score corresponds to better health status.
Measured: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Changes in oral-health related quality of life
Will be measured using Oral Health Impact Profile (OHIP-14) questionnaire .The OHIP-14 scores can range from 0 to 56 and are calculated by summing the ordinal values for the 14 items. The domain scores can range from 0 to 8. Higher OHIP-14 scores indicate worse and lower scores indicate better oral health related quality of life (OHRQol).
Measured: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Changes in functional limitation of the jaw.
Will be measured using jaw functional limitation scale (JFLS-20). The scores range from 1 to 200, with higher scores indicating deteriorating jaw function.
Measured: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Changes in Psychological Distress
Will be measured using general anxiety disorder (GAD-7) scale. Total score is obtained by adding score for each question (total points). A score of 8 or greater represents a reasonable cut-point for identifying probable cases of generalized anxiety disorder.
Measured: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Changes in Pain Catastrophizing
Will be measured using the Pain Catastrophizing Scale (PCS-DK). Consists of 13 items. Each item is ranged from 0-4. A high score corresponds to a high degree of pain catastrophizing.
Measured: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Changes in patients health
Measured using patient health questionnaire-15 (PHQ-15).Each item on the PHQ-15 is rated on a 3-point scale (0=not bothered at all; 1=bothered a little; 2= bothered a. lot). The total score can range from 0 to 30, with higher scores indicating greater severity of somatic symptoms.
Measured: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Changes in neuropathic pain characteristics
Measured using modified PainDetect questionnaire. The PainDetect questionnaire was slightly modified so that the oral components can also be added. It is scored from 0 to 38, with total scores of less than 12 considered to represent nociceptive pain, 13-18 possible neuropathic pain, and >19 representing >90% likelihood of neuropathic pain.
Measured: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2024
- Study start9 Sep 2022
- Primary completion11 May 2024
- Study completion11 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Neuropathic PainStudies of the same condition, open and under way.
- More trials run by University of AarhusThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- "n-of-1" single-blinded randomized controlled cross-over design: (A) active-sham-active-sham or (B) sham-active-sham-active.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Simple F Kothari, BDS, PhD, Principal investigator, University of Aarhus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06577649
- Sponsor's protocol ID
- 5771
- Status last verified
- Aug 2024
- First submitted
- 27 Aug 2024
- Last updated
- 5 Sep 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kothari SF, Dagsdottir LK, Kothari M, Blicher JU, Kumar A, Buchholtz PE, Ashkanian M, Svensson P. Effect of repetitive transcranial magnetic stimulation on altered perception of One's own face. Brain Stimul. 2020 May-Jun;13(3):554-561. doi: 10.1016/j.brs.2020.01.001. Epub 2020 Jan 8.
PubMed 32289676Kothari M, Renner N, Devendran AD, Alves-Costa S, Blicher JU, Svensson P, Kothari SF. A Series of N-of-1 Trials Characterizing Individual Responses to Theta-Burst Stimulation in Post-traumatic Trigeminal Neuropathic Pain. J Pain. 2026 Oct 2:106458. doi: 10.1016/j.jpain.2026.106458. Online ahead of print.
PubMed 42826822
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- From Pain in the Face to Perceptual Distortion: Exploring Mechanisms and Novel Treatment Strategies
- ClinicalTrials.gov ID
- NCT06577649
- Acronym / sponsor ID
- 5771
- Conditions
- Neuropathic Pain, Orofacial Pain
- Keywords
- Repetitive transcranial magnetic stimulation, N-of-1 trials, Perceptual distortion, Post-traumatic trigeminal neuropathic pain
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- 9 Sep 2022 (actual)
- Primary completion
- 11 May 2024 (actual)
- Study completion
- 11 Jul 2024 (actual)
- First posted
- 29 Aug 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.
Post-traumatic trigeminal neuropathic pain (PTNP) is "a unilateral or bilateral facial or oral pain following and caused by trauma to the trigeminal nerve(s), with other symptoms and/or clinical signs of trigeminal nerve dysfunction, and persisting or recurring for more than 3 months". PTNP may result from a major craniofacial/oral trauma or may be subsequent to relatively minor dental treatments such as teeth extractions, surgeries, root canal treatment. Patients suffering from this condition have a significantly reduced quality of life. Unfortunately, the currently available management modalities are associated with limited success and side effects.
Repetitive transcranial magnetic stimulation (rTMS), which is a safe, non-invasive brain stimulation technique has emerged as a potential treatment for chronic pain. In this study, the purpose is to explore the potential of rTMS in treating the persistent neuropathic pain by providing individualized treatment for the sufferers.
Detailed description
In addition to pain, a curious observation in people with PTNP is that they report that the painful facial area is "swollen" or "feels differently". There are often no clinical signs or physical differences present, hence such self-reported "illusions" may represent a kind of disrupted body image or a "perceptual distortion" of the face and can be speculated to contribute to the maintenance of facial pain. rTMS paradigms are being widely applied in both therapeutic and investigative studies.In this project, the aim is to employ continuous theta-burst stimulation (cTBS), an inhibitory rTMS paradigm, to evaluate its effect on pain perception and PD in people with PTNP.
In this project, people with PTNP (N=9) received a rTMS (50 Hz, 600 pulses for 40s) session/week as intervention for four consecutive weeks at the primary somatosensory cortex (face area) in a "n-of-1" single-blinded randomized controlled cross-over design: (A) active-sham-active-sham or (B) sham-active-sham-active. That is the same participant received both active and sham either in the (A) order or (B). Pain intensity and perceptual distortion (PD) as perceived size changes of the affected face area were measured at baseline, immediately, 60 mins after rTMS in each session and end of the session (a week after rTMS), one and three months after rTMS. Questionnaires on quality of life, jaw function, sleep quality were also assessed. Changes in pain and PD after each intervention were evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- "n-of-1" single-blinded randomized controlled cross-over design: (A) active-sham-active-sham or (B) sham-active-sham-active.
| Arm | Type | Receives |
|---|---|---|
| Active group | Active comparator | Device: Active repetitive transcranial magnetic stimulation (rTMS)Continuous theta burst stimulation |
| Sham group | Sham comparator | Device: Sham repetitive transcranial magnetic stimulation (sham rTMS)Sham repetitive transcranial magnetic stimulation (rTMS) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Persistent Post-traumatic trigeminal neuropathic pain patients for 6 months or longer
- Stable on analgesic medication
Key exclusion criteria (4 listed)
- past history of TMS therapy or TMS-related contraindications (pacemaker, epilepsy etc.).
- Major stroke
- Pregnancy
- Severe organic brain damage
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 |
|---|---|---|
| Active repetitive transcranial magnetic stimulation (rTMS)cTBS (50 Hz, 600 pulses, 80% resting motor threshold) for 40s was applied continuously as active rTMS at the face representation area of primary somatosensory cortex (S1) | Device | Active group |
| Sham repetitive transcranial magnetic stimulation (sham rTMS)A sham rTMS was applied using the same stimulation parameters as with cTBS, but using a placebo coil, which produced similar sound as the real coil. | Device | Sham group |
Primary outcome
Changes in pain intensity
Time frame: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention).
Changes in pain intensity from baseline to end of each session measured using self-reported pain dairy using a 0-10 visual analog scale (VAS; 0=no pain and 10=worst pain imaginable). The intervention (active and sham rTMS) were each given in 2 sessions. In total, the participant received 4 sessions of intervention.
Changes in perceptual distortion
Time frame: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention).
Perceptual distortion defined as perceived change in the size/shape of the affected face area will be measured using Numerical Rating Scale ranging from -100% through 0% to +100%, where 0% = no size change, -100% = half the size and +100% = double the size in comparison with non-affected side of face and drawings of the affected area. The changes will be measured from baseline to the end of each session as done for pain intensity.
8 secondary outcomes
Changes in sleep quality
Time frame: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Changes in perceived health or health related quality of life
Time frame: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Changes in oral-health related quality of life
Time frame: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Changes in functional limitation of the jaw.
Time frame: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Changes in Psychological Distress
Time frame: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Changes in Pain Catastrophizing
Time frame: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Changes in patients health
Time frame: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Changes in neuropathic pain characteristics
Time frame: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention), 1 and 3 months after intervention.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2024.
- Results publication: PubMed 32289676Kothari SF, Dagsdottir LK, Kothari M, Blicher JU, Kumar A, Buchholtz PE, Ashkanian M, Svensson P. Effect of repetitive transcranial magnetic stimulation on altered perception of One's own face. Brain Stimul. 2020 May-Jun;13(3):554-561. doi: 10.1016/j.brs.2020.01.001. Epub 2020 Jan 8.
- Derived from this study: PubMed 42826822Kothari M, Renner N, Devendran AD, Alves-Costa S, Blicher JU, Svensson P, Kothari SF. A Series of N-of-1 Trials Characterizing Individual Responses to Theta-Burst Stimulation in Post-traumatic Trigeminal Neuropathic Pain. J Pain. 2026 Oct 2:106458. doi: 10.1016/j.jpain.2026.106458. Online ahead of print.
- Individual participant dataSharing planned: No
Related trials for Neuropathic Pain
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Enrolling by invitationPhase 4
Low Dose Naltrexone Therapy for Complex Regional Pain Syndrome
Complex Regional Pain Syndrome, Chronic Pain
RecruitingPhase 2
Effectiveness of Phenotype-based Pain Management Guidelines for Head and Neck Cancer Related Pain: a Pilot Study
Cancer Pain, Orofacial Pain
RecruitingPhase 2
A Master Protocol Study (LY900028) of Multiple Intervention-Specific-Appendices (ISAs) in Participants With Chronic Pain
Osteoarthritis, Knee, Diabetic Neuropathic Pain
RecruitingObservational study
Trigeminal Neuralgia Electrophysiology
Trigeminal Neuralgia
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. This study is not recruiting at the moment.
Simple F Kothari, BDS, PhD principal investigator
University of Aarhus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active repetitive transcranial magnetic stimulation (rTMS) in people with Neuropathic Pain and Orofacial Pain, run by University of Aarhus at 1 site in Denmark.
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 2 inclusion and 4 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: finished, as of the sponsor's last update on 5 Sep 2024. 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 Denmark. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Changes in pain intensity (time frame: Prior to intervention at each session (baseline) to the end of that session (7 days after intervention).). 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 NCT06577649, which also lists 2 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 5 Sep 2024.