Non-invasive Personalized Transcranial Cortical Neurostimulation for Pain Relief
- Conditions
- Drug-resistant Neuropathic Pain
- Interventions
- Device: tDCS (Transcranial Direct Current Stimulation)Device: tACS (Transcranial Alternating Current Stimulation)
- Registration Number
- NCT06209645
- Lead Sponsor
- Hospices Civils de Lyon
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 50
- 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-
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description tACS then tDCS 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. tDCS then tACS tDCS (Transcranial Direct 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. tDCS then tACS 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 tDCS (Transcranial Direct 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.
- Primary Outcome Measures
Name Time Method Pain intensity measure 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.
- Secondary Outcome Measures
Name Time Method 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) 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.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) 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.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) 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.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) 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.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) 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.