Non-invasive Personalized Transcranial Cortical Neurostimulation for Pain Relief

NCT06209645 | Recruiting

• 2 other identifiers: 69HCL23_0810ID-RCB
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Drug-resistant Neuropathic Pain

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Percentage of responding patients Percentage of patients responding favorably to stimulation (Z-score <-2) after tACS and conventional tDCS.

  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.

  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.

  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.

  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 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)

Study Arms (2)

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.

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.

Device: tDCS (Transcranial Direct Current Stimulation); Device: tACS (Transcranial Alternating Current Stimulation)

Interventions

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 then tDCS; tDCS then tACS

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.

tACS then tDCS; tDCS then tACS

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Recipient or beneficiary of a social security scheme-

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Centre d'Evaluation et de Traitement de la Douleur, Hôpital Neurologique Pierre Wertheimer

Bron, 69677, France

RECRUITING

MeSH Terms

Interventions

Transcranial Direct Current Stimulation

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Charbel SALAMEH, MD

  Central Integration of pain lab (NeuroPain); Lyon Neurocience research center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charbel SALAMEH, MD

CONTACT

00 33 4 72 35 78 29; ext-charbel.salameh@chu-lyon.fr

GARCIA-LARREA Luis, MD., PhD

CONTACT

00 33 4 72 35 78 88; luis.garcia-larrea@univ-lyon1.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 6, 2023
• First Posted: January 17, 2024
• Study Start: April 10, 2025
• Primary Completion (Estimated): January 10, 2029
• Study Completion (Estimated): January 10, 2029
• Last Updated: May 8, 2026

Record last verified: 2026-05

Locations

FR (1)