Chronic Neuropathic PainNCT05593237
Transcranial Magnetic Stimulation for Chronic Neuropathic Pain
A study testing High Frequency rTMS and Low Frequency rTMS in people with Chronic Neuropathic Pain and Post-Stroke Pain, run by University of California, San Francisco at 1 site in United States.
Trial summary
Chronic neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system. It is highly prevalent, debilitating, and challenging to treat. Current available treatments have low efficacy, high side effect burden, and are prone to misuse and dependence. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chronic Neuropathic Pain, Post-Stroke Pain, Trigeminal Neuralgia
- What is being tested?
- High Frequency rTMS and Low Frequency rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Apr 2022to 30 Dec 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
- Meets Criteria for Chronic Neuropathic Pain (NP):
- "Pain caused by a lesion or disease of the somatosensory nervous system
- Intractable pain longer than 6 months after pain onset
- Baseline VAS score 30-94-mm
- Currently prescribed pain medication for NP, history of prior medication trials without adequate pain control, or refused treatments for individual reasons
- Continuous pain in face and/or extremities
Show all 13Show fewer
- Age 18-80
- Any gender and all ethnoracial categories
- Stable on chronic pain medications for 4 weeks prior to the study and agreeable to continue throughout the study. These medications include: Tricyclic antidepressants (e.g., nortriptyline, amitriptyline), SNRIs (e.g., duloxetine, venlafaxine), gabapentinoids (e.g., gabapentin, pregabalin), antiepileptics (e.g., valproic acid, carbamazepine, lamotrigine), and daily anti-inflammatories (e.g., meloxicam), among others (as determined by study physician at the time of screening). Note: Medications that are known to increase cortical excitability (e.g., buproprion, maprotiline, tricyclic antidepressants, classical antipsychotics) or to have an inhibitory effect on brain excitability (e.g., antiepileptics, benzodiazepines, and atypical antipsychotics), or any other medications with relative hazard for use in TMS will be allowed upon review of medications and/or motor threshold determination by TMS specialist.
- Participants may continue to take as-needed pain medications and record daily usage throughout the experiment
- Capacity to provide informed consent
- Ability to tolerate study procedures
- Successfully complete the screening forms without contraindications
Who cannot join
- Neurologic: Dementia, Severe neurocognitive disorder (MoCA < 22), Severe aphasia, Seizure disorder, certain structural brain lesions (e.g., intracranial mass lesions, hydrocephalus, sequelae of meningitis), or complete paralysis at target site
- Psychiatric: DSM Axis I disorder, Suicidal thoughts, prior psychosurgery, prior ECT
- Procedural: prior rTMS within 1 year of consent, enrollment in other clinical trial in the past 6 months
- TMS contraindications: implanted device; presence of metal in the head, including eyes and ears (excluding dental implants); certain tics; medications or systemic illness that predispose seizure risk
- Participants with an unstable physical, systemic, or metabolic disorder (e.g., unstable hypertension, cardiac disease)
- Females who are pregnant or nursing
- Inability to complete the research study
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSF Medical Center
San Francisco, California, 94158
About this study
Official title: A Pilot Trial of Longitudinal Repetitive Transcranial Magnetic Stimulation (rTMS) for Chronic Neuropathic Pain
Chronic neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system. It is highly prevalent, debilitating, and challenging to treat. Current available treatments have low efficacy, high side effect burden, and are prone to misuse and dependence. Emerging evidence suggests that the transition from acute to chronic neuropathic pain is associated with reorganization of central brain circuits involved in pain processing. Repetitive transcranial magnetic stimulation (rTMS) is a promising alternative treatment that uses focused magnetic pulses to non-invasively modulate brain activity, a strategy that can potentially circumvent the adverse effects of available treatments for pain. RTMS is FDA-approved for the treatment of major depressive disorder, obsessive-compulsive disorder, and migraine, and has been shown to reduce pain scores when applied to the contralateral motor cortex (M1). However, available studies of rTMS for chronic neuropathic pain typically show variable and often short-lived benefits, and many aspects of optimal treatment remain unknown, including ideal rTMS stimulation parameters, duration of treatment, and relationship to the underlying pain etiology. Here the investigators propose to evaluate the efficacy of high frequency rTMS to M1, the region with most evidence of benefit in chronic neuropathic pain, and to use functional magnetic resonance imaging (fMRI) to identify alternative rTMS targets for participants that do not respond to stimulation at M1. The central aim is to evaluate the pain relieving efficacy of multi-session high-frequency M1 TMS for pain. In secondary exploratory analyses, the investigator propose to investigate patient characteristic that are predictive of responsive to M1 rTMS and identify viable alternative stimulation targets in non-responders to M1 rTMS.
Read the detailed description
The investigators will recruit 20 patients diagnosed with chronic neuropathic pain for a randomized, single-blind, 2-arm crossover pilot TMS treatment trial. Participants will be recruited outpatients from departments of neurosurgery, neurology, and pain medicine at UCSF; patients referred from other hospitals or clinics as candidates of this trial. Baseline screening, clinical interviews, behavioral testing, and recording of pain scores will be performed in either the UCSF Nancy Friend Pritzker Psychiatry Building, UCSF Pain Management Center, or UCSF Mount Zion Hospital prior to the first treatment session. Eligible patients will be randomized to one of two stimulation frequencies: high frequency (10Hz) excitatory vs low frequency (1Hz) inhibitory repetitive transcranial magnetic stimulation (rTMS). We will use clinical and research TMS devices that have been cleared by the FDA for treating obsessive compulsive disorder and refractory major depressive disorder (located in the Pritzker Building) through a collaboration with Dr. Andrew Krystal (Director of UCSF Interventional Psychiatry Program and Co-Director of the TMS \& Neuromodulation Clinic) and Dr. Moses Lee (Director of OCD clinic) at UCSF.
Randomized patients will return for once daily rTMS sessions for 10 consecutive weekdays. On the first randomization visit, participants will record their current pain level using a visual analog scale (VAS), complete a variety of self-report scales (e.g., NIH PROMIS questionnaires, pain map, McGill Pain Questionnaire (MPQ), Pain Catastrophizing Scale (PCS), Pain Anxiety Symptom Scale (PASS), Beck Depression Inventory-II (BDI-II), WHO Disability Assessment Schedule (WHODAS), Patient Global Impression of Change (PGIC), and Pittsburgh Sleep Quality Index (PSQI)), and undergo a brain MRI session consisting of T1-weighted, T2-weighted, and diffusion tensor anatomical scans as well as functional MRI (fMRI) scans at rest and while rating spontaneous pain. Using single-pulse TMS, the investigators will estimate individual resting motor thresholds (RMT) of the affected extremity. Each treatment visit will consist of either: a series of thirty 10-Hz stimulations to the target brain regions at 90% RMT (each lasting 10 s with 50 s between stimulations, for a total of 3,000 pulses per visit) or thirty 1-Hz stimulations to the target brain regions at 90% RMT (total of 300 pulses per visit). Each treatment session will last ~30 min. Electromyography (EMG), heart rate and galvanic skin conductance will be recorded continuously throughout each session.
After completing the first 10 sessions, participants will have the option to receive additional stimulation with at either the same region or at a new target region, determined by each subject's baseline MRI scan, at the same frequency with the same schedule as the first session of treatment. Non-responders (<35% improvement of VAS scores) and those with relapse post-treatment to within 35% pre-treatment baseline pain severity will cross over to the new target arm. Participants will be followed for 6-months to evaluate the duration of benefit with follow up assessments at 1 week, 1 month, and 6 months.
- Conditions
- Chronic Neuropathic Pain, Post-Stroke Pain, Trigeminal Neuralgia, Nerve Injury, Spinal Cord Injuries, Pain, Postoperative
- Being tested
- High Frequency rTMS, Low Frequency rTMS
- Keywords
- Pain, Neuropathic Pain, TMS, Neuromodulation
- Medical subject headings
- Trigeminal Neuralgia, Spinal Cord Injuries, Pain, Postoperative, Complex Regional Pain Syndromes, Neuralgia, Postherpetic, Radiculopathy, Pain, Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High Frequency rTMSDevice
Stimulation provided at 10 Hz over target brain regions in thirty trains consisting of 10 seconds of stimulation alternating with 50 seconds of rest (3,000 pulses/session)
Low Frequency rTMSDevice
Stimulation provided at 1 Hz over target brain regions in thirty trains consisting of 10 seconds of stimulation alternating with 50 seconds of rest (300 pulses/session)
| Study group | Role | What they receive |
|---|---|---|
| High Frequency rTMS | Experimental | High frequency 10 Hz stimulation of motor cortex (M1) Receives: Device: High Frequency rTMS |
| Low Frequency rTMS | Active comparator | Low frequency 1 Hz stimulation of motor cortex (M1) Receives: Device: Low Frequency rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pain Intensity Over 2 weeks
Change in visual analog scores (VAS) of pain intensity on 0-100 mm scale. 0 indicates no pain, 100 indicates most pain imaginable.
Measured: Baseline and 2 weeks
Secondary outcomes (9)
Change in Pain Intensity Over 6 months
Change in visual analog scores (VAS) of pain intensity on 0-100 mm scale. 0 indicates no pain, 100 indicates most pain imaginable.
Measured: Baseline and 6 months
Change in Pain Unpleasantness Over 2 weeks
Change in visual analog scores (VAS) of pain unpleasantness on 0-100 mm scale. 0 indicates not bothersome at all, 100 indicates most bothersome pain imaginable.
Measured: Baseline and 2 weeks
Change in Pain Unpleasantness Over 6 months
Change in visual analog scores (VAS) of pain unpleasantness on 0-100 mm scale. 0 indicates not bothersome at all, 100 indicates most bothersome pain imaginable.
Measured: Baseline and 6 months
Percent Responders
Proportion of patients in each group with >50% reduction in pain intensity VAS
Measured: Baseline and 2 weeks
Percent Responders
Proportion of patients in each group with >50% reduction in pain intensity VAS
Measured: Baseline and 6 months
Change in medication use
Change in daily as-needed medication use from baseline, in number of doses per day.
Measured: Baseline and 2 weeks
Change in medication use
Change in daily as-needed medication use from baseline, in number of doses per day.
Measured: Baseline and 6 months
Change in McGill Pain Questionnaire (MPQ) Pain scores
The McGill Pain Questionnaire is a validated measure of multiple domains of pain processing, including sensory and affective pain processing as well as nociceptive and neuropathic pain. Scores range from 0-45 with 0 indicating low pain and 45 indicating high pain.
Measured: Baseline and 6 months
Change in Beck Depression Inventory (BDI-II) Scores
Validated measure of clinical depression symptoms to quantify and track mood over time. Scores index depression severity and range from 0-63: 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.
Measured: Baseline and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2022
- Study start25 Apr 2022
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Chronic Neuropathic PainStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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
- Parallel groups
- Model description
- Blinded, randomized pilot TMS treatment trial
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Facial Pain Research Foundation
- Responsible party
- Sponsor
- Investigators
- Julian C Motzkin, MD/PhD, Principal investigator, University of California, San FranciscoPrasad Shirvalkar, MD/PHD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05593237
- Sponsor's protocol ID
- 21-33344
- Status last verified
- Oct 2026
- First submitted
- 20 Oct 2022
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Apkarian AV, Baliki MN, Geha PY. Towards a theory of chronic pain. Prog Neurobiol. 2009 Feb;87(2):81-97. doi: 10.1016/j.pneurobio.2008.09.018. Epub 2008 Oct 5.
PubMed 18952143Arendt-Nielsen L, Morlion B, Perrot S, Dahan A, Dickenson A, Kress HG, Wells C, Bouhassira D, Drewes AM. Assessment and manifestation of central sensitisation across different chronic pain conditions. Eur J Pain. 2018 Feb;22(2):216-241. doi: 10.1002/ejp.1140. Epub 2017 Nov 5.
PubMed 29105941Chou YH, Ton That V, Chen AY, Sundman M, Huang YZ. TMS-induced seizure cases stratified by population, stimulation protocol, and stimulation site: A systematic literature search. Clin Neurophysiol. 2020 May;131(5):1019-1020. doi: 10.1016/j.clinph.2020.02.008. Epub 2020 Mar 3. No abstract available.
PubMed 32193163Hosomi K, Sugiyama K, Nakamura Y, Shimokawa T, Oshino S, Goto Y, Mano T, Shimizu T, Yanagisawa T, Saitoh Y; TEN-P11-01 investigators. A randomized controlled trial of 5 daily sessions and continuous trial of 4 weekly sessions of repetitive transcranial magnetic stimulation for neuropathic pain. Pain. 2020 Feb;161(2):351-360. doi: 10.1097/j.pain.0000000000001712.
PubMed 31593002Lefaucheur JP, Andre-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipovic SR, Hummel FC, Jaaskelainen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schonfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014 Nov;125(11):2150-2206. doi: 10.1016/j.clinph.2014.05.021. Epub 2014 Jun 5.
PubMed 25034472Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, Filipovic SR, Grefkes C, Hasan A, Hummel FC, Jaaskelainen SK, Langguth B, Leocani L, Londero A, Nardone R, Nguyen JP, Nyffeler T, Oliveira-Maia AJ, Oliviero A, Padberg F, Palm U, Paulus W, Poulet E, Quartarone A, Rachid F, Rektorova I, Rossi S, Sahlsten H, Schecklmann M, Szekely D, Ziemann U. Corrigendum to "Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018)" [Clin. Neurophysiol. 131 (2020) 474-528]. Clin Neurophysiol. 2020 May;131(5):1168-1169. doi: 10.1016/j.clinph.2020.02.003. Epub 2020 Feb 19. No abstract available.
PubMed 32122766Lerner AJ, Wassermann EM, Tamir DI. Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Clin Neurophysiol. 2019 Aug;130(8):1409-1416. doi: 10.1016/j.clinph.2019.03.016. Epub 2019 Apr 6.
PubMed 31104898Leung A, Shirvalkar P, Chen R, Kuluva J, Vaninetti M, Bermudes R, Poree L, Wassermann EM, Kopell B, Levy R; and the Expert Consensus Panel. Transcranial Magnetic Stimulation for Pain, Headache, and Comorbid Depression: INS-NANS Expert Consensus Panel Review and Recommendation. Neuromodulation. 2020 Apr;23(3):267-290. doi: 10.1111/ner.13094. Epub 2020 Mar 25.
PubMed 32212288O'Connell NE, Marston L, Spencer S, DeSouza LH, Wand BM. Non-invasive brain stimulation techniques for chronic pain. Cochrane Database Syst Rev. 2018 Apr 13;4(4):CD008208. doi: 10.1002/14651858.CD008208.pub5.
PubMed 29652088Rossi S, Antal A, Bestmann S, Bikson M, Brewer C, Brockmoller J, Carpenter LL, Cincotta M, Chen R, Daskalakis JD, Di Lazzaro V, Fox MD, George MS, Gilbert D, Kimiskidis VK, Koch G, Ilmoniemi RJ, Lefaucheur JP, Leocani L, Lisanby SH, Miniussi C, Padberg F, Pascual-Leone A, Paulus W, Peterchev AV, Quartarone A, Rotenberg A, Rothwell J, Rossini PM, Santarnecchi E, Shafi MM, Siebner HR, Ugawa Y, Wassermann EM, Zangen A, Ziemann U, Hallett M; basis of this article began with a Consensus Statement from the IFCN Workshop on "Present, Future of TMS: Safety, Ethical Guidelines", Siena, October 17-20, 2018, updating through April 2020. Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clin Neurophysiol. 2021 Jan;132(1):269-306. doi: 10.1016/j.clinph.2020.10.003. Epub 2020 Oct 24.
PubMed 33243615
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial of Longitudinal Repetitive Transcranial Magnetic Stimulation (rTMS) for Chronic Neuropathic Pain
- ClinicalTrials.gov ID
- NCT05593237
- Acronym / sponsor ID
- 21-33344
- Conditions
- Chronic Neuropathic Pain, Post-Stroke Pain, Trigeminal Neuralgia, Nerve Injury, Spinal Cord Injuries, Pain, Postoperative
- Keywords
- Pain, Neuropathic Pain, TMS, Neuromodulation
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Facial Pain Research Foundation
- Study start
- 25 Apr 2022 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 25 Oct 2022 (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.
Chronic neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system. It is highly prevalent, debilitating, and challenging to treat. Current available treatments have low efficacy, high side effect burden, and are prone to misuse and dependence. Emerging evidence suggests that the transition from acute to chronic neuropathic pain is associated with reorganization of central brain circuits involved in pain processing. Repetitive transcranial magnetic stimulation (rTMS) is a promising alternative treatment that uses focused magnetic pulses to non-invasively modulate brain activity, a strategy that can potentially circumvent the adverse effects of available treatments for pain. RTMS is FDA-approved for the treatment of major depressive disorder, obsessive-compulsive disorder, and migraine, and has been shown to reduce pain scores when applied to the contralateral motor cortex (M1). However, available studies of rTMS for chronic neuropathic pain typically show variable and often short-lived benefits, and many aspects of optimal treatment remain unknown, including ideal rTMS stimulation parameters, duration of treatment, and relationship to the underlying pain etiology. Here the investigators propose to evaluate the efficacy of high frequency rTMS to M1, the region with most evidence of benefit in chronic neuropathic pain, and to use functional magnetic resonance imaging (fMRI) to identify alternative rTMS targets for participants that do not respond to stimulation at M1. The central aim is to evaluate the pain relieving efficacy of multi-session high-frequency M1 TMS for pain. In secondary exploratory analyses, the investigator propose to investigate patient characteristic that are predictive of responsive to M1 rTMS and identify viable alternative stimulation targets in non-responders to M1 rTMS.
Detailed description
The investigators will recruit 20 patients diagnosed with chronic neuropathic pain for a randomized, single-blind, 2-arm crossover pilot TMS treatment trial. Participants will be recruited outpatients from departments of neurosurgery, neurology, and pain medicine at UCSF; patients referred from other hospitals or clinics as candidates of this trial. Baseline screening, clinical interviews, behavioral testing, and recording of pain scores will be performed in either the UCSF Nancy Friend Pritzker Psychiatry Building, UCSF Pain Management Center, or UCSF Mount Zion Hospital prior to the first treatment session. Eligible patients will be randomized to one of two stimulation frequencies: high frequency (10Hz) excitatory vs low frequency (1Hz) inhibitory repetitive transcranial magnetic stimulation (rTMS). We will use clinical and research TMS devices that have been cleared by the FDA for treating obsessive compulsive disorder and refractory major depressive disorder (located in the Pritzker Building) through a collaboration with Dr. Andrew Krystal (Director of UCSF Interventional Psychiatry Program and Co-Director of the TMS \& Neuromodulation Clinic) and Dr. Moses Lee (Director of OCD clinic) at UCSF.
Randomized patients will return for once daily rTMS sessions for 10 consecutive weekdays. On the first randomization visit, participants will record their current pain level using a visual analog scale (VAS), complete a variety of self-report scales (e.g., NIH PROMIS questionnaires, pain map, McGill Pain Questionnaire (MPQ), Pain Catastrophizing Scale (PCS), Pain Anxiety Symptom Scale (PASS), Beck Depression Inventory-II (BDI-II), WHO Disability Assessment Schedule (WHODAS), Patient Global Impression of Change (PGIC), and Pittsburgh Sleep Quality Index (PSQI)), and undergo a brain MRI session consisting of T1-weighted, T2-weighted, and diffusion tensor anatomical scans as well as functional MRI (fMRI) scans at rest and while rating spontaneous pain. Using single-pulse TMS, the investigators will estimate individual resting motor thresholds (RMT) of the affected extremity. Each treatment visit will consist of either: a series of thirty 10-Hz stimulations to the target brain regions at 90% RMT (each lasting 10 s with 50 s between stimulations, for a total of 3,000 pulses per visit) or thirty 1-Hz stimulations to the target brain regions at 90% RMT (total of 300 pulses per visit). Each treatment session will last ~30 min. Electromyography (EMG), heart rate and galvanic skin conductance will be recorded continuously throughout each session.
After completing the first 10 sessions, participants will have the option to receive additional stimulation with at either the same region or at a new target region, determined by each subject's baseline MRI scan, at the same frequency with the same schedule as the first session of treatment. Non-responders (<35% improvement of VAS scores) and those with relapse post-treatment to within 35% pre-treatment baseline pain severity will cross over to the new target arm. Participants will be followed for 6-months to evaluate the duration of benefit with follow up assessments at 1 week, 1 month, and 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Blinded, randomized pilot TMS treatment trial
| Arm | Type | Receives |
|---|---|---|
| High Frequency rTMS | Experimental | Device: High Frequency rTMSHigh frequency 10 Hz stimulation of motor cortex (M1) |
| Low Frequency rTMS | Active comparator | Device: Low Frequency rTMSLow frequency 1 Hz stimulation of motor cortex (M1) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Meets Criteria for Chronic Neuropathic Pain (NP):
- Age 18-80
- Any gender and all ethnoracial categories
- Stable on chronic pain medications for 4 weeks prior to the study and agreeable to continue throughout the study. These medications include: Tricyclic antidepressants (e.g., nortriptyline, amitriptyline), SNRIs (e.g., duloxetine, venlafaxine), gabapentinoids (e.g., gabapentin, pregabalin), antiepileptics (e.g., valproic acid, carbamazepine, lamotrigine), and daily anti-inflammatories (e.g., meloxicam), among others (as determined by study physician at the time of screening). Note: Medications that are known to increase cortical excitability (e.g., buproprion, maprotiline, tricyclic antidepressants, classical antipsychotics) or to have an inhibitory effect on brain excitability (e.g., antiepileptics, benzodiazepines, and atypical antipsychotics), or any other medications with relative hazard for use in TMS will be allowed upon review of medications and/or motor threshold determination by TMS specialist.
- Participants may continue to take as-needed pain medications and record daily usage throughout the experiment
Key exclusion criteria (7 listed)
- Neurologic: Dementia, Severe neurocognitive disorder (MoCA < 22), Severe aphasia, Seizure disorder, certain structural brain lesions (e.g., intracranial mass lesions, hydrocephalus, sequelae of meningitis), or complete paralysis at target site
- Psychiatric: DSM Axis I disorder, Suicidal thoughts, prior psychosurgery, prior ECT
- Procedural: prior rTMS within 1 year of consent, enrollment in other clinical trial in the past 6 months
- TMS contraindications: implanted device; presence of metal in the head, including eyes and ears (excluding dental implants); certain tics; medications or systemic illness that predispose seizure risk
- Participants with an unstable physical, systemic, or metabolic disorder (e.g., unstable hypertension, cardiac disease)
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 |
|---|---|---|
| High Frequency rTMSStimulation provided at 10 Hz over target brain regions in thirty trains consisting of 10 seconds of stimulation alternating with 50 seconds of rest (3,000 pulses/session) | Device | High Frequency rTMS |
| Low Frequency rTMSStimulation provided at 1 Hz over target brain regions in thirty trains consisting of 10 seconds of stimulation alternating with 50 seconds of rest (300 pulses/session) | Device | Low Frequency rTMS |
Primary outcome
Change in Pain Intensity Over 2 weeks
Time frame: Baseline and 2 weeks
Change in visual analog scores (VAS) of pain intensity on 0-100 mm scale. 0 indicates no pain, 100 indicates most pain imaginable.
9 secondary outcomes
Change in Pain Intensity Over 6 months
Time frame: Baseline and 6 months
Change in Pain Unpleasantness Over 2 weeks
Time frame: Baseline and 2 weeks
Change in Pain Unpleasantness Over 6 months
Time frame: Baseline and 6 months
Percent Responders
Time frame: Baseline and 2 weeks
Percent Responders
Time frame: Baseline and 6 months
Change in medication use
Time frame: Baseline and 2 weeks
Change in medication use
Time frame: Baseline and 6 months
Change in McGill Pain Questionnaire (MPQ) Pain scores
Time frame: Baseline and 6 months
Change in Beck Depression Inventory (BDI-II) Scores
Time frame: Baseline and 6 months
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 14 Oct 2026.
- Background: PubMed 18952143Apkarian AV, Baliki MN, Geha PY. Towards a theory of chronic pain. Prog Neurobiol. 2009 Feb;87(2):81-97. doi: 10.1016/j.pneurobio.2008.09.018. Epub 2008 Oct 5.
- Background: PubMed 29105941Arendt-Nielsen L, Morlion B, Perrot S, Dahan A, Dickenson A, Kress HG, Wells C, Bouhassira D, Drewes AM. Assessment and manifestation of central sensitisation across different chronic pain conditions. Eur J Pain. 2018 Feb;22(2):216-241. doi: 10.1002/ejp.1140. Epub 2017 Nov 5.
- Background: PubMed 32193163Chou YH, Ton That V, Chen AY, Sundman M, Huang YZ. TMS-induced seizure cases stratified by population, stimulation protocol, and stimulation site: A systematic literature search. Clin Neurophysiol. 2020 May;131(5):1019-1020. doi: 10.1016/j.clinph.2020.02.008. Epub 2020 Mar 3. No abstract available.
- Background: PubMed 31593002Hosomi K, Sugiyama K, Nakamura Y, Shimokawa T, Oshino S, Goto Y, Mano T, Shimizu T, Yanagisawa T, Saitoh Y; TEN-P11-01 investigators. A randomized controlled trial of 5 daily sessions and continuous trial of 4 weekly sessions of repetitive transcranial magnetic stimulation for neuropathic pain. Pain. 2020 Feb;161(2):351-360. doi: 10.1097/j.pain.0000000000001712.
- Background: PubMed 25034472Lefaucheur JP, Andre-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipovic SR, Hummel FC, Jaaskelainen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schonfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014 Nov;125(11):2150-2206. doi: 10.1016/j.clinph.2014.05.021. Epub 2014 Jun 5.
- Background: PubMed 32122766Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, Filipovic SR, Grefkes C, Hasan A, Hummel FC, Jaaskelainen SK, Langguth B, Leocani L, Londero A, Nardone R, Nguyen JP, Nyffeler T, Oliveira-Maia AJ, Oliviero A, Padberg F, Palm U, Paulus W, Poulet E, Quartarone A, Rachid F, Rektorova I, Rossi S, Sahlsten H, Schecklmann M, Szekely D, Ziemann U. Corrigendum to "Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018)" [Clin. Neurophysiol. 131 (2020) 474-528]. Clin Neurophysiol. 2020 May;131(5):1168-1169. doi: 10.1016/j.clinph.2020.02.003. Epub 2020 Feb 19. No abstract available.
- Background: PubMed 31104898Lerner AJ, Wassermann EM, Tamir DI. Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Clin Neurophysiol. 2019 Aug;130(8):1409-1416. doi: 10.1016/j.clinph.2019.03.016. Epub 2019 Apr 6.
- Background: PubMed 32212288Leung A, Shirvalkar P, Chen R, Kuluva J, Vaninetti M, Bermudes R, Poree L, Wassermann EM, Kopell B, Levy R; and the Expert Consensus Panel. Transcranial Magnetic Stimulation for Pain, Headache, and Comorbid Depression: INS-NANS Expert Consensus Panel Review and Recommendation. Neuromodulation. 2020 Apr;23(3):267-290. doi: 10.1111/ner.13094. Epub 2020 Mar 25.
- Background: PubMed 29652088O'Connell NE, Marston L, Spencer S, DeSouza LH, Wand BM. Non-invasive brain stimulation techniques for chronic pain. Cochrane Database Syst Rev. 2018 Apr 13;4(4):CD008208. doi: 10.1002/14651858.CD008208.pub5.
- Background: PubMed 33243615Rossi S, Antal A, Bestmann S, Bikson M, Brewer C, Brockmoller J, Carpenter LL, Cincotta M, Chen R, Daskalakis JD, Di Lazzaro V, Fox MD, George MS, Gilbert D, Kimiskidis VK, Koch G, Ilmoniemi RJ, Lefaucheur JP, Leocani L, Lisanby SH, Miniussi C, Padberg F, Pascual-Leone A, Paulus W, Peterchev AV, Quartarone A, Rotenberg A, Rothwell J, Rossini PM, Santarnecchi E, Shafi MM, Siebner HR, Ugawa Y, Wassermann EM, Zangen A, Ziemann U, Hallett M; basis of this article began with a Consensus Statement from the IFCN Workshop on "Present, Future of TMS: Safety, Ethical Guidelines", Siena, October 17-20, 2018, updating through April 2020. Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clin Neurophysiol. 2021 Jan;132(1):269-306. doi: 10.1016/j.clinph.2020.10.003. Epub 2020 Oct 24.
- 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. This study is not recruiting at the moment.
Julian C Motzkin, MD/PhD principal investigator
University of California, San Francisco
Prasad Shirvalkar, MD/PHD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High Frequency rTMS and Low Frequency rTMS in people with Chronic Neuropathic Pain and Post-Stroke Pain, run by University of California, San Francisco at 1 site 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 13 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: under way, not looking for participants, as of the sponsor's last update on 14 Oct 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 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?
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?
Change in Pain Intensity Over 2 weeks (time frame: Baseline and 2 weeks). 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 NCT05593237, which also lists 10 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 14 Oct 2026.