Personalized High-Definition tDCS Protocols for Chronic Pain Treatment
ConditionChronic Pain
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-75
SponsorIstituti Clinici Scientifici Maugeri SpA
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Diagnosis of chronic pain lasting for at least six months
Pain scores equal to or greater than 4 on Numerical Rating Scale (NRS) 0-10 on most days for the last 3 months
Pain unresponsive to conservative treatment such as pharmacological therapy and physiotherapy, and unresponsive to minimally invasive treatments such as peripheral nerve blocks or neuromodulation or steroid epidural injections, when appropriate
Age between 18 and 75
Disqualifiers
History of seizure disorders
Active malignancy
Implanted medical devices and/or metallic implants in the head or neck region
Cranial abnormalities
Trial design
Design model
Parallel
Treatments tested in this trial
Anodal High-Definition transcranial Direct Current Stimulation
DeviceParticipants 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.
Cathodal High-Definition transcranial Direct Current Stimulation
DeviceParticipants 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)
DeviceParticipants 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.
Treatment groups
144 Participants
are divided into 3 treatment groupsGroup A: CathodalActive comparator 1 intervention
Group B: AnodalActive comparator 1 intervention
Group C: ShamSham comparator 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Baseline; Up to 3 weeks; After 3 monthsSecondary outcomes
1
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.
Time frame
Baseline; Up to 3 weeksSponsors and contacts
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Istituti Clinici Scientifici Maugeri SpA
Lead sponsor
University of Milano Bicocca
Collaborator
IRCCS ISMETT Palermo
Collaborator
University of Palermo
Collaborator
Source ClinicalTrials.gov