Non-invasive Personalized Transcranial Cortical Neurostimulation for Pain Relief (PERSOSTIM)

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.

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 Overview

• Status: Recruiting
• Conditions: Drug-resistant Neuropathic Pain
• Intervention / Treatment: Device: tDCS (Transcranial Direct Current Stimulation); Device: tACS (Transcranial Alternating Current Stimulation)

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Charbel SALAMEH, MD; Phone Number: 00 33 4 72 35 78 29; Email: ext-charbel.salameh@chu-lyon.fr
• Study Contact Backup: Name: GARCIA-LARREA Luis, MD., PhD; Phone Number: 00 33 4 72 35 78 88; Email: luis.garcia-larrea@univ-lyon1.fr

Study Locations

• France
  • Bron, France, 69677
    • Recruiting
    • Centre d'Evaluation et de Traitement de la Douleur, Hôpital Neurologique Pierre Wertheimer
    • Contact: Charbel SALAMEH, M.D.; Phone Number: +33 4 72 35 78 29; Email: charbel.salameh@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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-

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tDCS then tACS; 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.	Device: 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 (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.
Experimental: tACS then tDCS; 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.	Device: 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 (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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	daily from the beginning until the end of the protocol (15 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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)

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Charbel SALAMEH, MD, Central Integration of pain lab (NeuroPain); Lyon Neurocience research center

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2025
• Primary Completion (Estimated): January 10, 2029
• Study Completion (Estimated): January 10, 2029

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: January 15, 2024
• First Posted (Actual): January 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Therapeutics; Behavioral Disciplines and Activities; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Transcranial Direct Current Stimulation
• Other Study ID Numbers: 69HCL23_0810; ID-RCB (Other Identifier: 2025-A02239-40)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No