Drug-resistant Neuropathic PainPERSOSTIMNCT06209645
Non-invasive Personalized Transcranial Cortical Neurostimulation for Pain Relief
A study testing tDCS (Transcranial Direct Current Stimulation) and tACS (Transcranial Alternating Current Stimulation) in people with Drug-resistant Neuropathic Pain, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Neuropathic pain is a public health problem with less than 50% of patients being relieved by drug treatments. Surgically implanted motor cortex stimulation represents an invasive therapeutic solution capable of relieving a significant proportion of drug-resistant patients (1 in 2); it cannot, however, be offered to… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Drug-resistant Neuropathic Pain
- What is being tested?
- tDCS (Transcranial Direct Current Stimulation) and tACS (Transcranial Alternating Current Stimulation)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- 10 Apr 2025to 10 Jan 2029
- 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
- Aged 18 to 80 years
- Neuropathic pain of more than one year's duration1
- Failed treatment with tricyclic or tetracyclic antidepressants, antiepileptics and a combination of morphine and a serotonin (5HT) norepinephrine (NA2) reuptake inhibitor, in the absence of contraindication.
- Average pain intensity of at least 4/10 in the month preceding the inclusion visit.
- Recipient or beneficiary of a social security scheme-
Who cannot join
- Chronic non-neuropathic pain or pain associated with progressive pathology, active epilepsy, unhealed scalp wound, impaired comprehension or communication that prevents subjective daily and weekly assessments.
- Active epilepsy, treated or not
- Unhealed scalp wound adjacent to EEG recording electrodes or transcranial stimulation application (contraindication to Medical Device (DM) use)
- Pregnant or breast-feeding women
- Inability to understand or follow the ins and outs of the study, in particular the need to assess pain intensity on a daily basis or to trace it, possibly with the help of a third party (comprehension or communication disorders).
- People under guardianship, curatorship or legal protection
- Persons deprived of their liberty, persons under psychiatric care and persons admitted to a health or social establishment for purposes other than clinical investigation
- Participation in other research interfering with the present study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Centre d'Evaluation et de Traitement de la Douleur, Hôpital Neurologique Pierre Wertheimer
Bron, 69677
Charbel SALAMEH, M.D., +33 4 72 35 78 29, charbel.salameh@chu-lyon.fr
About this study
Official title: Non-invasive Analgesic Stimulation of the Patient's Motor Cortex With an Oscillating Electric Current at the Dominant Frequency Recorded by EEG
Neuropathic pain is a public health problem with less than 50% of patients being relieved by drug treatments.
Surgically implanted motor cortex stimulation represents an invasive therapeutic solution capable of relieving a significant proportion of drug-resistant patients (1 in 2); it cannot, however, be offered to all patients, and is not morbidity-free.
Read more
Non-invasive motor cortex stimulation techniques have been refined over the last decade, in particular transcranial repetitive magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), which provide pain relief among almost half of drug-resistant patients with few or no side effects.
To be efficient, cortical stimulation requires the activation of multiple distant networks involved in the cognitive and motivational response to pain; stimulation frequency is a crucial parameter for activating these mechanisms. The match between cortical stimulation frequency and the intrinsic neuronal frequency of the stimulated cortex has recently been suggested as a key determinant of clinical effect. Indeed, the transmission efficiency of an oscillatory network increases when its intrinsic frequency matches that of the stimulus applied to it. Given that human sensorimotor networks spontaneously oscillate at frequencies around 10 and 20 Hertz (Hz), this match could underlie the superior efficacy of transcranial stimulation at these frequencies.
The hypothesis of the study is that the analgesic effect of cortical stimulation will be enhanced if the stimulation frequency resonates with the spontaneous oscillations of the underlying cortex, thus facilitating its connectivity with the remote structures involved in pain control. The investigators propose to test this hypothesis in a population of patients with drug-resistant neuropathic pain, referred to the Pain Evaluation and Treatment Center (CETD) of the Neurological hospital, at the Hospices Civils de Lyon. The overall aim of the project is to compare the efficacy of stimulation at each individual's own rate of oscillation of the motor cortex, against a "classic" stimulation protocol, and against placebo stimulation.
- Conditions
- Drug-resistant Neuropathic Pain
- Being tested
- tDCS (Transcranial Direct Current Stimulation), tACS (Transcranial Alternating Current Stimulation)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tDCS (Transcranial Direct Current Stimulation)Device
The tDCS group will be treated with non-invasive motor cortex stimulation. A two-minute EEG recording will be made before each session, using the same electrodes as for stimulation. Anodal stimulation of 2,0 mA will be delivered over the motor area contralateral to the painful region (C4 or C3 according to the international 10-20 system). The return electrode will be placed over the fronto-polar region (FP1 or FP2) ipsilateral to the painful region. If pain is bilateral, the most painful region will be chosen to be treated.
tACS (Transcranial Alternating Current Stimulation)Device
The tACS group will be treated with non-invasive motor cortex stimulation. The stimulation series comprises six sessions spaced 2 weeks apart, the first session being placebo. A two-minute EEG recording will be made before each session, using the same electrodes as for stimulation. Stimulation frequency will be set according to the dominant frequency recorded over the motor area. Anodal stimulation of 2,0 mA will be delivered over the motor area contralateral to the painful region (C4 or C3 according to the international 10-20 system). The return electrode will be placed over the fronto-polar region (FP1 or FP2) ipsilateral to the painful region.
| Study group | Role | What they receive |
|---|---|---|
| tDCS then tACS | Experimental | This group is made up of adult patients with drug-resistant neuropathic pain, who started with tDCS stimulation, followed by tACS stimulation, in accordance with randomization. Each series of each modality comprises 6 sessions spaced 2 weeks apart, the first session being in placebo mode and the following 5 in active mode. Each session lasts 20 minutes. In placebo mode, a 2 miliampere (mA) current is delivered for 30 seconds at the start and at the end of the session, to prevent the patient noticing the difference between placebo and active stimulation. In active mode, the 2mA current is delivered for the duration of the session. Receives: Device: tDCS (Transcranial Direct Current Stimulation); Device: tACS (Transcranial Alternating Current Stimulation) |
| tACS then tDCS | Experimental | This group is made up of adult patients with drug-resistant neuropathic pain, who started with tACS stimulation, followed by tDCS stimulation, in accordance with randomization. Each series of each modality comprises 6 sessions spaced 2 weeks apart, the first session being in placebo mode and the following 5 in active mode. Each session lasts 20 minutes. In placebo mode, a 2mA current is delivered for 30 seconds at the start and at the end of the session, to prevent the patient noticing the difference between placebo and active stimulation. In active mode, the 2mA current is delivered for the duration of the session. Receives: Device: tDCS (Transcranial Direct Current Stimulation); Device: tACS (Transcranial Alternating Current Stimulation) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain intensity measure
Comparison of weekly standardized averages of the Numerical rating scale (NRS) values at the end of tACS versus tDCS versus placebo stimulation sessions.
Pain scale measurement:
pain scale : 1 the minimum and 10 maximum value, 10 the higher score mean a worse outcome.
Measured: daily from the beginning until the end of the protocol (15 months)
Secondary outcomes (5)
Percentage of responding patients Percentage of patients responding favorably to stimulation (Z-score <-2) after tACS and conventional tDCS.
The response is considered favorable if on the NRS scale, compared with the baseline of each participant, there is a pain improvement of:
- more than 30% or
- more than 2 points or
- more than 2 Standard Deviation
Pain scale measurement:
pain scale : 1 the minimum and 10 maximum value, 10 the higher score means a worse outcome.
Measured: daily from the beginning until the end of the protocol (15 months)
Patient's Global Impression of Change (PGIC) Comparison of weekly standardized values of the PGIC at the end of tACS versus tDCS versus placebo stimulation sessions.
The PGIC is a seven-points scale that allows the patient to rate their overall impression of change
1 minimum value and 7 maximum value, and 7 higher score means worse result.
Measured: one a week from the beginning until the end of the protocol (15 months)
Fatigue score Comparison of weekly standardized averages of the fatigue score values at the end of tACS versus tDCS versus placebo stimulation sessions.
The fatigue score is a ten-points (from 0 to 10) scale that allows the patient to rate their fatigue
fatigue scale : 1 the minimum and 10 maximum value, 10 the higher score means a worse outcome.
Measured: daily from the beginning until the end of the protocol (15 months)
Sleep score Comparison of weekly standardized averages of the sleep score values at the end of tACS versus tDCS versus placebo stimulation sessions.
The sleep score is a ten-points (from 0 to 10) scale that allows the patient to rate their quality of sleep with 0= bad quality and 10 = excellent quality
Sleep scale : 1 the minimum and 10 maximum value, 10 the higher score means a worse outcome.
Measured: daily from the beginning until the end of the protocol (15 months)
Sympathetic Skin Response (SSR) measurement Variation, in patients with hyperalgesia/allodynia, of Sympathetic Skin Response after treatment with tACS versus tDCS versus placebo.
SSR is an objective measure of patient's arousal. For patients suffering from allodynia, SSR will be measured after touch (brush) and/or heat (laser) stimulation on sensitized region and a symmetrical non-sensitised region
SSR is expressed in mV(millivolt). It is a record of a physiological measurement. The minimum value corresponds to the absence of a response greater than the background recorded by the electrodes. There is no maximum value. The change in response is significant if there is a change greater than 30% from baseline.
Measured: SSR will be measured in allodynic patients before each stimulation and evaluation session, starting with the first stimulation session until the end of the protocol (15 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2024
- Study start10 Apr 2025
- Primary completion10 Jan 2029 (estimated)
- Study completion10 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug-resistant Neuropathic PainStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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
- The study involves the use of transcranial electrical stimulation applied to the motor cortex at each subject's own cortical rhythm. The rhythm is previously obtained by electroencephalographic (EEG) recording. Fifty adult patients, recruited by the Pain Evaluation and Treatment Center of the Neurological hospital, at the Hospices Civils de Lyon, suffering from drug-resistant neuropathic pain for more than 12 months. The stimulation (tACS) will be compared head-to-head with another reference active stimulation modality, namely anodal direct current stimulation (tDCS) of the motor cortex. The 2 types of active stimulation will be performed in cross-over mode, in randomized order, and compared with placebo stimulation. Each stimulation modality will comprise 6 sessions spaced 2 weeks apart, with the first session in placebo mode and the next 5 in active mode.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Charbel SALAMEH, MD, Principal investigator, Central Integration of pain lab (NeuroPain); Lyon Neurocience research center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06209645
- Sponsor's protocol ID
- 69HCL23_0810
- Other IDs
- ID-RCB
- Acronym
- PERSOSTIM
- Status last verified
- May 2026
- First submitted
- 6 Dec 2023
- Last updated
- 8 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Analgesic Stimulation of the Patient's Motor Cortex With an Oscillating Electric Current at the Dominant Frequency Recorded by EEG
- ClinicalTrials.gov ID
- NCT06209645
- Acronym / sponsor ID
- PERSOSTIM / 69HCL23_0810
- Conditions
- Drug-resistant Neuropathic Pain
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 10 Apr 2025 (actual)
- Primary completion
- 10 Jan 2029 (estimated)
- Study completion
- 10 Jan 2029 (estimated)
- First posted
- 17 Jan 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.
Neuropathic pain is a public health problem with less than 50% of patients being relieved by drug treatments.
Surgically implanted motor cortex stimulation represents an invasive therapeutic solution capable of relieving a significant proportion of drug-resistant patients (1 in 2); it cannot, however, be offered to all patients, and is not morbidity-free.
Non-invasive motor cortex stimulation techniques have been refined over the last decade, in particular transcranial repetitive magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), which provide pain relief among almost half of drug-resistant patients with few or no side effects.
To be efficient, cortical stimulation requires the activation of multiple distant networks involved in the cognitive and motivational response to pain; stimulation frequency is a crucial parameter for activating these mechanisms. The match between cortical stimulation frequency and the intrinsic neuronal frequency of the stimulated cortex has recently been suggested as a key determinant of clinical effect. Indeed, the transmission efficiency of an oscillatory network increases when its intrinsic frequency matches that of the stimulus applied to it. Given that human sensorimotor networks spontaneously oscillate at frequencies around 10 and 20 Hertz (Hz), this match could underlie the superior efficacy of transcranial stimulation at these frequencies.
The hypothesis of the study is that the analgesic effect of cortical stimulation will be enhanced if the stimulation frequency resonates with the spontaneous oscillations of the underlying cortex, thus facilitating its connectivity with the remote structures involved in pain control. The investigators propose to test this hypothesis in a population of patients with drug-resistant neuropathic pain, referred to the Pain Evaluation and Treatment Center (CETD) of the Neurological hospital, at the Hospices Civils de Lyon. The overall aim of the project is to compare the efficacy of stimulation at each individual's own rate of oscillation of the motor cortex, against a "classic" stimulation protocol, and against placebo stimulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- The study involves the use of transcranial electrical stimulation applied to the motor cortex at each subject's own cortical rhythm. The rhythm is previously obtained by electroencephalographic (EEG) recording. Fifty adult patients, recruited by the Pain Evaluation and Treatment Center of the Neurological hospital, at the Hospices Civils de Lyon, suffering from drug-resistant neuropathic pain for more than 12 months. The stimulation (tACS) will be compared head-to-head with another reference active stimulation modality, namely anodal direct current stimulation (tDCS) of the motor cortex. The 2 types of active stimulation will be performed in cross-over mode, in randomized order, and compared with placebo stimulation. Each stimulation modality will comprise 6 sessions spaced 2 weeks apart, with the first session in placebo mode and the next 5 in active mode.
| Arm | Type | Receives |
|---|---|---|
| tDCS then tACS | Experimental | Device: tDCS (Transcranial Direct Current Stimulation), Device: tACS (Transcranial Alternating Current Stimulation)This group is made up of adult patients with drug-resistant neuropathic pain, who started with tDCS stimulation, followed by tACS stimulation, in accordance with randomization. Each series of each modality comprises 6 sessions spaced 2 weeks apart, the first session being in placebo mode and the following 5 in active mode. Each session lasts 20 minutes. In placebo mode, a 2 miliampere (mA) current is delivered for 30 seconds at the start and at the end of the session, to prevent the patient noticing the difference between placebo and active stimulation. In active mode, the 2mA current is delivered for the duration of the session. |
| tACS then tDCS | Experimental | Device: tDCS (Transcranial Direct Current Stimulation), Device: tACS (Transcranial Alternating Current Stimulation)This group is made up of adult patients with drug-resistant neuropathic pain, who started with tACS stimulation, followed by tDCS stimulation, in accordance with randomization. Each series of each modality comprises 6 sessions spaced 2 weeks apart, the first session being in placebo mode and the following 5 in active mode. Each session lasts 20 minutes. In placebo mode, a 2mA current is delivered for 30 seconds at the start and at the end of the session, to prevent the patient noticing the difference between placebo and active stimulation. In active mode, the 2mA current is delivered for the duration of the session. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Aged 18 to 80 years
- Neuropathic pain of more than one year's duration1
- Failed treatment with tricyclic or tetracyclic antidepressants, antiepileptics and a combination of morphine and a serotonin (5HT) norepinephrine (NA2) reuptake inhibitor, in the absence of contraindication.
- Average pain intensity of at least 4/10 in the month preceding the inclusion visit.
- Recipient or beneficiary of a social security scheme-
Key exclusion criteria (8 listed)
- Chronic non-neuropathic pain or pain associated with progressive pathology, active epilepsy, unhealed scalp wound, impaired comprehension or communication that prevents subjective daily and weekly assessments.
- Active epilepsy, treated or not
- Unhealed scalp wound adjacent to EEG recording electrodes or transcranial stimulation application (contraindication to Medical Device (DM) use)
- Pregnant or breast-feeding women
- Inability to understand or follow the ins and outs of the study, in particular the need to assess pain intensity on a daily basis or to trace it, possibly with the help of a third party (comprehension or communication disorders).
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 |
|---|---|---|
| tDCS (Transcranial Direct Current Stimulation)The tDCS group will be treated with non-invasive motor cortex stimulation. A two-minute EEG recording will be made before each session, using the same electrodes as for stimulation. Anodal stimulation of 2,0 mA will be delivered over the motor area contralateral to the painful region (C4 or C3 according to the international 10-20 system). The return electrode will be placed over the fronto-polar region (FP1 or FP2) ipsilateral to the painful region. If pain is bilateral, the most painful region will be chosen to be treated. | Device | tACS then tDCS, tDCS then tACS |
| tACS (Transcranial Alternating Current Stimulation)The tACS group will be treated with non-invasive motor cortex stimulation. The stimulation series comprises six sessions spaced 2 weeks apart, the first session being placebo. A two-minute EEG recording will be made before each session, using the same electrodes as for stimulation. Stimulation frequency will be set according to the dominant frequency recorded over the motor area. Anodal stimulation of 2,0 mA will be delivered over the motor area contralateral to the painful region (C4 or C3 according to the international 10-20 system). The return electrode will be placed over the fronto-polar region (FP1 or FP2) ipsilateral to the painful region. | Device | tACS then tDCS, tDCS then tACS |
Primary outcome
Pain intensity measure
Time frame: daily from the beginning until the end of the protocol (15 months)
Comparison of weekly standardized averages of the Numerical rating scale (NRS) values at the end of tACS versus tDCS versus placebo stimulation sessions. Pain scale measurement: pain scale : 1 the minimum and 10 maximum value, 10 the higher score mean a worse outcome.
5 secondary outcomes
Percentage of responding patients Percentage of patients responding favorably to stimulation (Z-score <-2) after tACS and conventional tDCS.
Time frame: daily from the beginning until the end of the protocol (15 months)
Patient's Global Impression of Change (PGIC) Comparison of weekly standardized values of the PGIC at the end of tACS versus tDCS versus placebo stimulation sessions.
Time frame: one a week from the beginning until the end of the protocol (15 months)
Fatigue score Comparison of weekly standardized averages of the fatigue score values at the end of tACS versus tDCS versus placebo stimulation sessions.
Time frame: daily from the beginning until the end of the protocol (15 months)
Sleep score Comparison of weekly standardized averages of the sleep score values at the end of tACS versus tDCS versus placebo stimulation sessions.
Time frame: daily from the beginning until the end of the protocol (15 months)
Sympathetic Skin Response (SSR) measurement Variation, in patients with hyperalgesia/allodynia, of Sympathetic Skin Response after treatment with tACS versus tDCS versus placebo.
Time frame: SSR will be measured in allodynic patients before each stimulation and evaluation session, starting with the first stimulation session until the end of the protocol (15 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 8 May 2026.
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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.
Charbel SALAMEH, MD principal investigator
Central Integration of pain lab (NeuroPain); Lyon Neurocience research center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing tDCS (Transcranial Direct Current Stimulation) and tACS (Transcranial Alternating Current Stimulation) in people with Drug-resistant Neuropathic Pain, run by Hospices Civils de Lyon at 1 site in France.
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 5 inclusion and 8 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 8 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 France. 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 Charbel SALAMEH, MD (00 33 4 72 35 78 29, ext-charbel.salameh@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain intensity measure (time frame: daily from the beginning until the end of the protocol (15 months)). 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 8 May 2026.