Chronic PainPersoNINpainNCT07247552
Personalized Treatment by rTMS in Chronic Pain - Study2
A study testing rTMS to M1 in people with Chronic Pain, run by Aalborg University at 1 site in Denmark.
Trial summary
Previous research has shown the effectiveness of magnetic stimulation of the brain as a supplemental treatment for various conditions, such as depression and chronic pain. However, the application of magnetic stimulation has been standardized across patients without considering individual differences. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chronic Pain
- What is being tested?
- rTMS to M1
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Apr 2025to Jun 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Presence of chronic pain (present most of the days for more than 3 months).
- Pain with a mean pain intensity between 3-9 on a 0-10 pain scale (where 0 means no pain and 10 means the worst pain imaginable).
- Speak and understand English or Danish
Who cannot join
- Pregnant or breastfeeding
- Current uncontrolled major depression as the main diagnosis
- Current history of substance abuse
- Lack of ability to cooperate, to fully understand the protocol or any difficulty in filling out questionnaires (e.g., due to language or cognitive problems)
- Formal contraindications to TMS application (presence of epilepsy, cranial implanted ferromagnetic devices, e.g., intracranial neurostimulator or cochlear implants, tattoos with metal ink on the face or permanent make up with metal in the face )
- Unable to answer the "Transcranial Magnetic Stimulation Adult Safety Screen" screening questionnaire.
- Participation in other research protocols within 1 month before the inclusion.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Daniel C de Andrade contact
Denmark1 site, 1 recruiting
- Recruiting
Aalborg University
Gistrup, 9260
Margit M Bach, Dr, +45 9137 3170, forskning.dca@hst.aau.dk
Daniel C de Andrade, Prof
About this study
Official title: Personalized Pain Treatment by Transcranial Magnetic Stimulation in Patients With Chronic Pain: A Prospective Interventional Study With Embedded Predictive Biomarker Evaluation
Previous research has shown the effectiveness of magnetic stimulation of the brain as a supplemental treatment for various conditions, such as depression and chronic pain. However, the application of magnetic stimulation has been standardized across patients without considering individual differences. This one-size-fits-all approach results in only half of the patients benefiting from the treatment, with the other half seeing no improvement in their symptoms. Therefore, a study on individuals with chronic pain will be performed to explore how magnetic stimulation treatments can be tailored to each person. This will involve analysing brain signal measurements before the start of the therapy and adjusting/personalizing the magnetic stimulations to each individual person.
Read the detailed description
This is a prospective, single-arm interventional study designed to evaluate the predictive value of a neurophysiological biomarker for repetitive transcranial magnetic stimulation (rTMS) response in chronic pain patients. The project aims to test if the effects of non-pharmacological, non-invasive pain treatment can be enhanced by employing brain connectivity information to guide the application of rTMS. Previous efficacy and safety trials have supported that current best practice for rTMS for pain relief in chronic pain patients, is applied to one cortical area: primary motor cortex (M1). However, only around 50% respond to the treatment. Since there is no current strategy to know which patient will respond to treatment, patients with chronic pain end up undergoing trial and error strategies, which delay their improvement. This is actually not different from challenges related to pharmacological treatment, where each medication only relieves pain in 30-40% of patients, and the choice of each medication is based on "trial-and-error basis".
Several strategies currently aim to provide a more individualized strategy for choosing analgesic interventions based on patient-related information. To allow for the design of efficacy trials in the future, the present project is based on a proof-of-concept, mechanistic design. It will employ M1 rTMS stimulation for pain reduction. However, based on everyone's brain signals as read by EEG recorded before the start of the treatment it will be determined whether the patient is most likely to respond or not. Therefore, before receiving a full rTMS treatment, patients will undergo a neurophysiological screening session using single-pulse TMS-EEG. Single-pulse TMS and EEG have been routinely used in the clinic as a part of the neurophysiological assessment of patients for decades but have not yet been used in the association as an attempt to try to guide who will become a responder to the treatment. In the screening session, single pulses TMS will be applied to the primary network hub used as current best-practice in therapeutic rTMS: M1. Concomitantly, the EEG oscillatory activity of this cortical area will be recorded, and the brain connectivity state will be assessed. By using information derived from a patient´s brain connectivity state using transcranial magnetic stimulation with electroencephalography (TMS-EEG), it will be determined if the participant is most likely to respond or not. High oscillatory activity is expected to result in becoming a non-responder.
A total of 90 subjects with chronic pain will be included in a double-blind, randomized two parallel-arm study aiming to be able to accurately predict who will become a responder and a non-responder based on high oscillatory activity.
In the initial baseline measurement, the subjects will fill out questionnaires and undergo neurophysiological assessments which include rest EEG, TMS-EEG of M1, rTMS-EEG, followed by a repetition of TMS-EEG of M1 and rest EEG. After this baseline measurement, the subjects will receive daily rTMS sessions targeting M1 (called induction phase) for 5 consecutive days (Monday to Friday). Each of the 5 daily stimulations will last 30 minutes, of which 15 minutes will be under treatment.
The induction phase will be followed by a 7-week maintenance phase, with 1 rTMS session per week (totalling 7 rTMS sessions). At the end of the maintenance phase, primary and secondary outcomes (questionnaires) will be collected to investigate the efficacy of the rTMS treatments. These questionnaires will also be sent to participants 12 weeks following end of treatment. A random subsample of 30 participants will be asked if they would like to participate in a second 3-hour neurophysiological assessment to investigate the changes in brain connectivity.
- Conditions
- Chronic Pain
- Being tested
- rTMS to M1
- Keywords
- Pain, Neurologic Manifestations, Signs and Symptoms, Pathological Conditions, Signs and Symptoms, Chronic Pain, Transcranial Magnetic Stimulation, Neuromodulation
- Medical subject headings
- Chronic Pain, Pain, Neurologic Manifestations, Signs and Symptoms, Pathological Conditions, Signs and Symptoms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMS to M1Device
- The rTMS intervention consists of 10-Hz rTMS. Thirty trains of ten seconds with an interval of twenty seconds between trains will be delivered, as traditionally performed. Each train includes 100 pulses, and the total number of pulses will be 3,000 given in 15 minutes. All patients will receive 14 sessions of rTMS.
| Study group | Role | What they receive |
|---|---|---|
| Classical rTMS to M1 | Active comparator | This is a prospective, single-arm interventional study designed to evaluate the predictive value of a neurophysiological biomarker for rTMS response in chronic pain patients. Patients will be allocated to two groups according to their baseline M1 connectivity at baseline in a 1:1 proportion. Patients with "low" connectivity will be compared to controls having "high" connectivity. All patients will receive repetitive transcranial magnetic stimulation (rTMS) to the primary cortex (M1). Low connectivity will be defined by TMS-EEG evoked responses. Responses to a single pulse of TMS delivered to M1 before therapy. TMS-EEG responses will be analysed by phase- and power-based metrics such as global mean field power and inter-trial coherence in the alpha band, according to previous studies. The study main hypothesis is that pre-therapy M1 low connectivity is a predictor of response to M1 rTMS. Receives: Device: rTMS to M1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain intensity (Visual analogue scale)
The '0' represents 'no pain' at all, and '100' represents the 'worst possible pain' that the individual can imagine.
Measured: VAS will be assessed before treatment and post intervention. Responders are those with ≥30% pain reduction, based on the difference in VAS the last 24 hours at the end of maintenance compared to average pain intensity the week before baseline assessment.
Secondary outcomes (4)
Patients' Global Impression of Change
The questionnaire assesses the individual's impression of change after an intervention.
The Likert scale is asking whether 'After the beginning of this study, my overall state of health is': with the options of 'Very much improved', 'Much improved', 'Minimally improved', 'No change', 'Minimally worse', 'Much worse'.
Measured: Patients' Global Impression of Change will be investigated before the treatment, at the end of the course of treatment (8 weeks of treatment), and again after 3 months following the end of treatment.
Short Brief Pain Inventory
9 item self-administered questionnaire used to evaluate the severity of a patient's pain and the impact of this pain on the patient's daily functioning. Items such as pain severity and Pain Interference Score can be calculated as well as number of affected body areas.
Measured: Short Brief Pain Inventory changes will be investigated before the treatment, at the end of the course of treatment (8 weeks of treatment), and again after 3 months following the end of treatment.
Short McGill Pain Questionnaire
A comprehensive multidimensional tool that assesses the three main aspects of pain: sensory discriminative, affective-motivational, and cognitive-evaluative. Words describing pain is presented and the patient has to choose whether it is recognisable in mild, moderate or severe way and it has the option of 'none'.
Measured: Short McGill Pain Questionnaire changes will be investigated before the treatment, at the end of the course of treatment (8 weeks of treatment), and again after 3 months following the end of treatment.
Quality of sleep (VAS)
A VAS scale to determine 'how did you sleep last night' ranging from 0 ('poor') to 10 ('great').
Measured: Sleep VAS changes will be investigated before the treatment, at the end of the course of treatment (8 weeks of treatment), and again after 3 months following the end of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2025
- Study start1 Apr 2025
- Primary completionMar 2026 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aalborg University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Margit Midtgaard Bach, Aalborg University
- Investigators
- Margit M Bach, PhD, Principal investigator, Aalborg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07247552
- Sponsor's protocol ID
- N-20230076-3
- Acronym
- PersoNINpain
- Status last verified
- Nov 2025
- First submitted
- 18 Nov 2025
- Last updated
- 1 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Personalized Pain Treatment by Transcranial Magnetic Stimulation in Patients With Chronic Pain: A Prospective Interventional Study With Embedded Predictive Biomarker Evaluation
- ClinicalTrials.gov ID
- NCT07247552
- Acronym / sponsor ID
- PersoNINpain / N-20230076-3
- Conditions
- Chronic Pain
- Keywords
- Pain, Neurologic Manifestations, Signs and Symptoms, Pathological Conditions, Signs and Symptoms, Chronic Pain, Transcranial Magnetic Stimulation, Neuromodulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Aalborg UniversityUniversity, hospital or other
- Study start
- 1 Apr 2025 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 25 Nov 2025 (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.
Previous research has shown the effectiveness of magnetic stimulation of the brain as a supplemental treatment for various conditions, such as depression and chronic pain. However, the application of magnetic stimulation has been standardized across patients without considering individual differences. This one-size-fits-all approach results in only half of the patients benefiting from the treatment, with the other half seeing no improvement in their symptoms. Therefore, a study on individuals with chronic pain will be performed to explore how magnetic stimulation treatments can be tailored to each person. This will involve analysing brain signal measurements before the start of the therapy and adjusting/personalizing the magnetic stimulations to each individual person.
Detailed description
This is a prospective, single-arm interventional study designed to evaluate the predictive value of a neurophysiological biomarker for repetitive transcranial magnetic stimulation (rTMS) response in chronic pain patients. The project aims to test if the effects of non-pharmacological, non-invasive pain treatment can be enhanced by employing brain connectivity information to guide the application of rTMS. Previous efficacy and safety trials have supported that current best practice for rTMS for pain relief in chronic pain patients, is applied to one cortical area: primary motor cortex (M1). However, only around 50% respond to the treatment. Since there is no current strategy to know which patient will respond to treatment, patients with chronic pain end up undergoing trial and error strategies, which delay their improvement. This is actually not different from challenges related to pharmacological treatment, where each medication only relieves pain in 30-40% of patients, and the choice of each medication is based on "trial-and-error basis".
Several strategies currently aim to provide a more individualized strategy for choosing analgesic interventions based on patient-related information. To allow for the design of efficacy trials in the future, the present project is based on a proof-of-concept, mechanistic design. It will employ M1 rTMS stimulation for pain reduction. However, based on everyone's brain signals as read by EEG recorded before the start of the treatment it will be determined whether the patient is most likely to respond or not. Therefore, before receiving a full rTMS treatment, patients will undergo a neurophysiological screening session using single-pulse TMS-EEG. Single-pulse TMS and EEG have been routinely used in the clinic as a part of the neurophysiological assessment of patients for decades but have not yet been used in the association as an attempt to try to guide who will become a responder to the treatment. In the screening session, single pulses TMS will be applied to the primary network hub used as current best-practice in therapeutic rTMS: M1. Concomitantly, the EEG oscillatory activity of this cortical area will be recorded, and the brain connectivity state will be assessed. By using information derived from a patient´s brain connectivity state using transcranial magnetic stimulation with electroencephalography (TMS-EEG), it will be determined if the participant is most likely to respond or not. High oscillatory activity is expected to result in becoming a non-responder.
A total of 90 subjects with chronic pain will be included in a double-blind, randomized two parallel-arm study aiming to be able to accurately predict who will become a responder and a non-responder based on high oscillatory activity.
In the initial baseline measurement, the subjects will fill out questionnaires and undergo neurophysiological assessments which include rest EEG, TMS-EEG of M1, rTMS-EEG, followed by a repetition of TMS-EEG of M1 and rest EEG. After this baseline measurement, the subjects will receive daily rTMS sessions targeting M1 (called induction phase) for 5 consecutive days (Monday to Friday). Each of the 5 daily stimulations will last 30 minutes, of which 15 minutes will be under treatment.
The induction phase will be followed by a 7-week maintenance phase, with 1 rTMS session per week (totalling 7 rTMS sessions). At the end of the maintenance phase, primary and secondary outcomes (questionnaires) will be collected to investigate the efficacy of the rTMS treatments. These questionnaires will also be sent to participants 12 weeks following end of treatment. A random subsample of 30 participants will be asked if they would like to participate in a second 3-hour neurophysiological assessment to investigate the changes in brain connectivity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Classical rTMS to M1 | Active comparator | Device: rTMS to M1This is a prospective, single-arm interventional study designed to evaluate the predictive value of a neurophysiological biomarker for rTMS response in chronic pain patients. Patients will be allocated to two groups according to their baseline M1 connectivity at baseline in a 1:1 proportion. Patients with "low" connectivity will be compared to controls having "high" connectivity. All patients will receive repetitive transcranial magnetic stimulation (rTMS) to the primary cortex (M1). Low connectivity will be defined by TMS-EEG evoked responses. Responses to a single pulse of TMS delivered to M1 before therapy. TMS-EEG responses will be analysed by phase- and power-based metrics such as global mean field power and inter-trial coherence in the alpha band, according to previous studies. The study main hypothesis is that pre-therapy M1 low connectivity is a predictor of response to M1 rTMS. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Presence of chronic pain (present most of the days for more than 3 months).
- Pain with a mean pain intensity between 3-9 on a 0-10 pain scale (where 0 means no pain and 10 means the worst pain imaginable).
- Speak and understand English or Danish
Key exclusion criteria (7 listed)
- Pregnant or breastfeeding
- Current uncontrolled major depression as the main diagnosis
- Current history of substance abuse
- Lack of ability to cooperate, to fully understand the protocol or any difficulty in filling out questionnaires (e.g., due to language or cognitive problems)
- Formal contraindications to TMS application (presence of epilepsy, cranial implanted ferromagnetic devices, e.g., intracranial neurostimulator or cochlear implants, tattoos with metal ink on the face or permanent make up with metal in the face )
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 |
|---|---|---|
| rTMS to M1• The rTMS intervention consists of 10-Hz rTMS. Thirty trains of ten seconds with an interval of twenty seconds between trains will be delivered, as traditionally performed. Each train includes 100 pulses, and the total number of pulses will be 3,000 given in 15 minutes. All patients will receive 14 sessions of rTMS. | Device | Classical rTMS to M1 |
Primary outcome
Pain intensity (Visual analogue scale)
Time frame: VAS will be assessed before treatment and post intervention. Responders are those with ≥30% pain reduction, based on the difference in VAS the last 24 hours at the end of maintenance compared to average pain intensity the week before baseline assessment.
The '0' represents 'no pain' at all, and '100' represents the 'worst possible pain' that the individual can imagine.
4 secondary outcomes
Patients' Global Impression of Change
Time frame: Patients' Global Impression of Change will be investigated before the treatment, at the end of the course of treatment (8 weeks of treatment), and again after 3 months following the end of treatment.
Short Brief Pain Inventory
Time frame: Short Brief Pain Inventory changes will be investigated before the treatment, at the end of the course of treatment (8 weeks of treatment), and again after 3 months following the end of treatment.
Short McGill Pain Questionnaire
Time frame: Short McGill Pain Questionnaire changes will be investigated before the treatment, at the end of the course of treatment (8 weeks of treatment), and again after 3 months following the end of treatment.
Quality of sleep (VAS)
Time frame: Sleep VAS changes will be investigated before the treatment, at the end of the course of treatment (8 weeks of treatment), and again after 3 months following the end of treatment.
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 1 Dec 2025.
- Individual participant dataSharing planned: No
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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.
Daniel C de Andrade contact
Margit M Bach, PhD principal investigator
Aalborg University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rTMS to M1 in people with Chronic Pain, run by Aalborg University 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 3 inclusion and 7 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 1 Dec 2025. 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. 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 Margit M Bach (+45 9137 3170, forskning.dca@hst.aau.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain intensity (Visual analogue scale) (time frame: VAS will be assessed before treatment and post intervention. Responders are those with ≥30% pain reduction, based on the difference in VAS the last 24 hours at the end of maintenance compared to average pain intensity the week before baseline assessment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Dec 2025.