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| ID | Type | Description | Link |
|---|---|---|---|
| PNRR-MCNT2-2023-12378259 | Other Grant/Funding Number | Italian Ministry of Health |
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| Name | Class |
|---|---|
| University of Milano Bicocca | OTHER |
| IRCCS ISMETT Palermo | UNKNOWN |
| University of Palermo | OTHER |
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This study aims to examine the use of neurostimulation as a potential adjuvant treatment for chronic pain. Among neurostimulation techniques, transcranial direct current stimulation (tDCS) represents a promising, yet not fully exploited, option. Recent methodological advances allow for increased intensity and focality of its effects through personalized high-definition tDCS protocols (HD-tDCS), enabling targeted stimulation of specific brain regions involved in pain and analgesia processing, such as the dorsal anterior cingulate cortex (dACC).
Based on this evidence, the specific objective of the study is to investigate the effect of an innovative HD-tDCS protocol (personalized using structural and functional magnetic resonance imaging (fMRI)), with stimulation applied to the dACC. The experimental design involves randomly assigning 144 patients with chronic pain to three groups, who will undergo an intensive treatment (five sessions in the same week) with cathodal, anodal, or sham (placebo) HD-tDCS.
Patient recruitment and treatment will be equally distributed between sites located in Lombardy (IRCCS Maugeri-Pavia; University of Milano-Bicocca; n=72) and Palermo (IRCCS ISMETT-Palermo; University of Palermo; n=72).
The effects of neurostimulation will be: a) evaluated using self-reported measures of physical and social functioning (Brief Pain Inventory, BPI; primary outcome) before and after treatment, and at follow-up assessments at 3 weeks and 3 months; b) interpreted in relation to underlying neurophysiological changes, as revealed by the high spatial and temporal resolution provided, respectively, by fMR) and by transcranial magnetic stimulation-evoked potentials combined with electroencephalographic recording (TMS-EEG) before and after treatment (secondary outcome).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cathodal | Active Comparator | Cathodal HD-tDCS |
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| Anodal | Active Comparator | Anodal HD-tDCS |
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| Sham | Sham Comparator | Sham HD-tDCS |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anodal High-Definition transcranial Direct Current Stimulation | Device | Participants will receive 5 stimulation sessions in a week, with the HD-tDCS setup including 6 electrodes (3 anode + 3 cathode electrodes) delivering a total current of 2mA. The spatial configuration of the six electrodes is aimed to induce the maximum intensity of stimulation at the target stereotactic coordinate, based on the modeling of estimated distribution of electric fields. The active stimulation lasts for 20 minutes. |
| Measure | Description | Time Frame |
|---|---|---|
| Reduction of perceived pain | We aim to assess the effect of a personalized (MRI-based) HD-tDCS protocol targeting dACC on clinical measures of perceived chronic pain. To this purpose, patients will be randomly assigned to 3 groups, each undergoing either cathodal, anodal or sham HD-tDCS treatment. Neurostimulation effects will be assessed with self-reported measures of perceived pain, collected via validated subjective functional questionnaires at 3 timepoints: before and after a 1-week (5 sessions) treatment, and at a 3 months follow-up assessment. The BPI score will be indeed considered the primary outcome measure for assessing the effect of HD-tDCS treatment, which will be deemed effective if a 30% reduction of pain intensity and interference on the BPI will be reached. The same statistical approach will be applied to the other clinical scales administered. In case of normality violations, data will be analyzed by means of non-parametric tests. | Baseline; Up to 3 weeks; After 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in pain-related neural sensitivity measured with fMRI and TMS-EEG | Participants will undergo both fMRI and TMS-EEG sessions at the two main timepoints (pre- and post-treatment). For both techniques, data will be collected during a) resting-state (cross-fixation); b) observation of pain-related/unrelated facial expressions and bodily stimulations (Jauniaux et al., 2019). The T1-weighted MRI image collected on the pre-treatment session will be used for personalized targeting/modeling of HD-tDCS electric fields, and for neuronavigation in TMS-EEG sessions. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Milano-Bicocca | Recruiting | Milan | 20126 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | Roth, Y., Padberg, F., and Zangen, A. (2007). Transcranial magnetic stimulation of deep brain regions: principles and methods. ADVANCES IN BIOLOGICAL PSYCHIATRY-BASEL-, 23(R), 204. | ||
| Background | Garg, A., and Mago, V. (2021). Role of machine learning in medical research: A survey. Computer science review, 40, 100370. | ||
| 36066447 | Background | Xiong HY, Cao YQ, Du SH, Yang QH, He SY, Wang XQ. Effects of High-Definition Transcranial Direct Current Stimulation Targeting the Anterior Cingulate Cortex on the Pain Thresholds: A Randomized Controlled Trial. Pain Med. 2023 Jan 4;24(1):89-98. doi: 10.1093/pm/pnac135. | |
| 33566301 |
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| Cathodal High-Definition transcranial Direct Current Stimulation | Device | Participants will receive 5 stimulation sessions in a week, with the HD-tDCS setup including 6 electrodes (3 anode + 3 cathode electrodes) delivering a total current of 2mA. The spatial configuration of the six electrodes is aimed to induce the maximum intensity of stimulation at the target stereotactic coordinate, based on the modeling of estimated distribution of electric fields. The active stimulation lasts for 20 minutes. In cathodal sessions, polarity is reversed. |
|
| Sham (No Treatment) | Device | Participants will receive 5 stimulation sessions in a week, with the HD-tDCS setup including 6 electrodes (3 anode + 3 cathode electrodes) delivering a total current of 2mA. The spatial configuration of the six electrodes is aimed to induce the maximum intensity of stimulation at the target stereotactic coordinate, based on the modeling of estimated distribution of electric fields. In sham sessions, the duration is also 20 minutes but participants are unaware that the stimulation intensity gradually ramps down to 0 mA after 30 seconds and then ramps up again during the final 30 seconds. |
|
| Baseline; Up to 3 weeks |
| Irccs Ismett | Recruiting | Palermo | 90127 | Italy |
|
| University of Palermo | Recruiting | Palermo | 90127 | Italy |
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| Istituti Clinici Scientifici Maugeri Spa Società Benefit | Recruiting | Pavia | 27100 | Italy |
|
| Background |
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| ID | Term |
|---|---|
| D059350 | Chronic Pain |
| ID | Term |
|---|---|
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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