Chronic PainPRECISE-PainNCT07266103
Mechanistic Study of Personalized rTMS in Chronic Pain
A study testing Classical repetitive trancranial magnetic stimulation to M1 and Personalized Target Arm in people with Chronic Pain, run by Aalborg University at 1 site in Denmark.
Trial summary
Previous research has demonstrated that repetitive magnetic brain stimulation can be an effective adjunctive treatment for several conditions, including chronic pain. However, current stimulation protocols are typically standardized and do not account for individual variability in brain function. 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?
- Classical repetitive trancranial magnetic stimulation to M1 and Personalized Target Arm
- 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 Mar 2026to 31 May 2028
- 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 Ciampi De Andrade, MD, PhD contact
Denmark1 site, 1 recruiting
- Recruiting
Aalborg University
Gistrup, 9260
Enrico De Martino, MD, PhD, 91811183, edm@hst.aau.dk
About this study
Official title: Building on Previous Evidence: A Mechanistic Clinical Trial of Personalized rTMS for Chronic Pain
Previous research has demonstrated that repetitive magnetic brain stimulation can be an effective adjunctive treatment for several conditions, including chronic pain. However, current stimulation protocols are typically standardized and do not account for individual variability in brain function. This uniform, one-size-fits-all approach results in only about 40% of patients experiencing meaningful clinical benefit, while the remainder show little to no improvement. To address this limitation, the present study will investigate how magnetic stimulation can be tailored to individuals with chronic pain. By analyzing each participant's brain signals prior to treatment, we aim to personalize stimulation parameters to better match individual neural characteristics and potentially enhance therapeutic outcomes. The design of this study builds directly on the findings of a previous clinical trial.
Read the detailed description
This study builds directly on previous clinical findings identifying four cortical targets-primary motor cortex (M1), anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC) and the posterior insula (PSI)-as exhibiting neurophysiological properties potentially useful for guiding individualized repetitive transcranial magnetic stimulation (rTMS) target selection. Earlier results demonstrated that chronic pain patients with low alpha-band intertrial coherence (ITC) over M1 were more likely to respond to stimulation of M1, whereas patients with high alpha-band ITC showed a greater likelihood of responding to stimulation of PSI, ACC or DLPFC. These findings suggest that specific electroencephalography (EEG) connectivity markers may help predict the cortical target most likely to provide therapeutic benefit for an individual patient.
Building on this evidence, the present trial will classify participants according to their pre-treatment transcranial magnetic stimulation-electroencephalography (TMS-EEG) connectivity profiles and assign treatment to the cortical region with the highest predicted probability of clinical response.
A total of 90 patients with chronic pain will be enrolled in a double-blind, randomized, two-parallel-arm clinical trial comparing the analgesic effects of individualized target selection with those of the standard rTMS protocol. Participants will be randomized 1:1 to:
- Individualized targeting, in which the rTMS site is selected based on each participant's TMS-EEG connectivity profile
- Standard stimulation, representing the conventional rTMS approach for pain relief.
At baseline, participants will complete standardized questionnaires and undergo neurophysiological assessments, including single-pulse TMS-EEG for target classification. The induction phase will then begin, consisting of five consecutive daily rTMS sessions delivered Monday through Friday. Each session lasts 30 minutes, including 15 minutes of active stimulation.
The induction phase will be followed by a 7-week maintenance phase, during which participants receive one rTMS session per week (seven sessions in total). At the end of the maintenance phase, all outcome measures will be reassessed to evaluate treatment efficacy.
- Conditions
- Chronic Pain
- Being tested
- Classical repetitive trancranial magnetic stimulation to M1, Personalized Target Arm
- Keywords
- pain, TMS-EEG, rTMS
- Medical subject headings
- Chronic Pain, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Classical repetitive trancranial magnetic stimulation 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.
Personalized Target ArmDevice
The rTMS intervention consists of 10-Hz rTMS. Thirty trains of ten seconds will be delivered with an interval of twenty seconds between trains. Each train includes 100 pulses, and the total number of pulses will be 3,000 given in 15 minutes. The rTMS will be delivered to the optimal target
| Study group | Role | What they receive |
|---|---|---|
| Active Comparator : Classical rTMS | Active comparator | The patients will receive repetitive transcranial magnetic stimulation according to the classical treatment Receives: Device: Classical repetitive trancranial magnetic stimulation to M1 |
| Experimental: Personalized Target Arm | Experimental | The patients will receive repetitive transcranial magnetic stimulation (rTMS) to target showing the optimal connectivity during the TMS-EEG assessment one week before starting the treatment Receives: Device: Personalized Target Arm |
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: Visual analogue scale will be assessed before treatment, after 2 months, and again after 3 months. Responders are those with ≥30% pain reduction at the end of maintenance compared to average pain intensity the week before baseline assessment.
Secondary outcomes (4)
Quality of life (EQ-5D)
Quality of life (EQ-5D) is a standardized measure of health-related quality of life. This is the value derived from the 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). The EQ-5D-5L is a scale from 0 to 100, where 100 is the best health imaginable.
Measured: Quality of life changes will be investigated before the treatment, immediately after 2 months of treatment, and again after 3 months of treatment.
Patients' Global Impression of Change
The questionnaire assesses the individual's impression of change after an intervention. Minimum value: 1 = "Very much worse" and Maximum value: 7 = "Very much improved"
Measured: Patients' Global Impression of Change will be investigated before the treatment, immediately after 2 months of treatment, and again after 3 months 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
Measured: Short Brief Pain Inventory changes will be investigated before the treatment, immediately after 2 months of treatment, and again after 3 months of treatment.
Connectivity analysis
Electroencephalography recorded during single pulses of transcranial magnetic stimulation will be used to evaluate brain connectivity. Global mean field power, local mean field power, inter-trial coherence and event-related strectral perturbation will be the main outcome.
Measured: Connectivity changes will be investigated before the treatment and immediately after 2 months of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2025
- Study start1 Mar 2026
- Primary completion30 Jun 2027 (estimated)
- Study completion31 May 2028 (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
- Randomised
- Intervention model
- Parallel groups
- Model description
- When 50% of inclusion is completed, a preplanned interim futility analysis is scheduled to examine safety and the main outcome.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aalborg University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Enrico De Martino, Aalborg University
- Investigators
- Enrico De Martino, Principal investigator, Aalborg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07266103
- Sponsor's protocol ID
- N-20230076-4
- Acronym
- PRECISE-Pain
- Status last verified
- Nov 2025
- First submitted
- 18 Nov 2025
- Last updated
- 7 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 7 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Building on Previous Evidence: A Mechanistic Clinical Trial of Personalized rTMS for Chronic Pain
- ClinicalTrials.gov ID
- NCT07266103
- Acronym / sponsor ID
- PRECISE-Pain / N-20230076-4
- Conditions
- Chronic Pain
- Keywords
- pain, TMS-EEG, rTMS
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Aalborg UniversityUniversity, hospital or other
- Study start
- 1 Mar 2026 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 31 May 2028 (estimated)
- First posted
- 5 Dec 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 demonstrated that repetitive magnetic brain stimulation can be an effective adjunctive treatment for several conditions, including chronic pain. However, current stimulation protocols are typically standardized and do not account for individual variability in brain function. This uniform, one-size-fits-all approach results in only about 40% of patients experiencing meaningful clinical benefit, while the remainder show little to no improvement. To address this limitation, the present study will investigate how magnetic stimulation can be tailored to individuals with chronic pain. By analyzing each participant's brain signals prior to treatment, we aim to personalize stimulation parameters to better match individual neural characteristics and potentially enhance therapeutic outcomes. The design of this study builds directly on the findings of a previous clinical trial.
Detailed description
This study builds directly on previous clinical findings identifying four cortical targets-primary motor cortex (M1), anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC) and the posterior insula (PSI)-as exhibiting neurophysiological properties potentially useful for guiding individualized repetitive transcranial magnetic stimulation (rTMS) target selection. Earlier results demonstrated that chronic pain patients with low alpha-band intertrial coherence (ITC) over M1 were more likely to respond to stimulation of M1, whereas patients with high alpha-band ITC showed a greater likelihood of responding to stimulation of PSI, ACC or DLPFC. These findings suggest that specific electroencephalography (EEG) connectivity markers may help predict the cortical target most likely to provide therapeutic benefit for an individual patient.
Building on this evidence, the present trial will classify participants according to their pre-treatment transcranial magnetic stimulation-electroencephalography (TMS-EEG) connectivity profiles and assign treatment to the cortical region with the highest predicted probability of clinical response.
A total of 90 patients with chronic pain will be enrolled in a double-blind, randomized, two-parallel-arm clinical trial comparing the analgesic effects of individualized target selection with those of the standard rTMS protocol. Participants will be randomized 1:1 to:
- Individualized targeting, in which the rTMS site is selected based on each participant's TMS-EEG connectivity profile
- Standard stimulation, representing the conventional rTMS approach for pain relief.
At baseline, participants will complete standardized questionnaires and undergo neurophysiological assessments, including single-pulse TMS-EEG for target classification. The induction phase will then begin, consisting of five consecutive daily rTMS sessions delivered Monday through Friday. Each session lasts 30 minutes, including 15 minutes of active stimulation.
The induction phase will be followed by a 7-week maintenance phase, during which participants receive one rTMS session per week (seven sessions in total). At the end of the maintenance phase, all outcome measures will be reassessed to evaluate treatment efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- When 50% of inclusion is completed, a preplanned interim futility analysis is scheduled to examine safety and the main outcome.
| Arm | Type | Receives |
|---|---|---|
| Active Comparator : Classical rTMS | Active comparator | Device: Classical repetitive trancranial magnetic stimulation to M1The patients will receive repetitive transcranial magnetic stimulation according to the classical treatment |
| Experimental: Personalized Target Arm | Experimental | Device: Personalized Target ArmThe patients will receive repetitive transcranial magnetic stimulation (rTMS) to target showing the optimal connectivity during the TMS-EEG assessment one week before starting the treatment |
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 |
|---|---|---|
| Classical repetitive trancranial magnetic stimulation to M1The 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. | Device | Active Comparator : Classical rTMS |
| Personalized Target ArmThe rTMS intervention consists of 10-Hz rTMS. Thirty trains of ten seconds will be delivered with an interval of twenty seconds between trains. Each train includes 100 pulses, and the total number of pulses will be 3,000 given in 15 minutes. The rTMS will be delivered to the optimal target | Device | Experimental: Personalized Target Arm |
Primary outcome
Pain intensity (Visual analogue scale)
Time frame: Visual analogue scale will be assessed before treatment, after 2 months, and again after 3 months. Responders are those with ≥30% pain reduction 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
Quality of life (EQ-5D)
Time frame: Quality of life changes will be investigated before the treatment, immediately after 2 months of treatment, and again after 3 months of treatment.
Patients' Global Impression of Change
Time frame: Patients' Global Impression of Change will be investigated before the treatment, immediately after 2 months of treatment, and again after 3 months of treatment
Short Brief Pain Inventory
Time frame: Short Brief Pain Inventory changes will be investigated before the treatment, immediately after 2 months of treatment, and again after 3 months of treatment.
Connectivity analysis
Time frame: Connectivity changes will be investigated before the treatment and immediately after 2 months 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 7 May 2026.
- Individual participant dataSharing planned: No
Related trials for Chronic Pain
Recruiting
Empowered Relief® for Cancer Survivors With Chronic Pain
Chronic Pain Due to Cancer, Pain Catastrophizing
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruiting
Effect of Lumbar Stabilization Exercises With and Without YTWL (Scapular Stabilization Exercises) on Reducing Chronic Low Back Pain and Related Disability. A Randomized Clinical Trial,
Chronic Non Specific Mechanical Low Back Pain
Not yet recruiting
Comparing Non-Medicine Strategies for Improving Low Back Pain
Chronic Low-back Pain (cLBP), High-Impact Chronic Pain (HICP)
Not yet recruiting
Effect of Pectoral Nerve Block (PECS) Using Magnesium Sulfate Added to Dexamethasone on Quality of Recovery and Chronic Post-Mastectomy Pain
Breast Cancer, Postoperative 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.
Daniel Ciampi De Andrade, MD, PhD contact
Enrico De Martino 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 Classical repetitive trancranial magnetic stimulation to M1 and Personalized Target Arm 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 7 May 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 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 Enrico De Martino, MD, PhD (+4591811183, edm@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: Visual analogue scale will be assessed before treatment, after 2 months, and again after 3 months. Responders are those with ≥30% pain reduction 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 7 May 2026.