Personalized High-Definition tDCS Protocols for Chronic Pain Treatment

February 24, 2026 updated by: Istituti Clinici Scientifici Maugeri SpA

Innovative Neuromodulation Treatments for Chronic Pain: Assessing and Predicting the Effects of Personalized High-Definition Protocols for Transcranial Direct Current Stimulation (HD-tDCS)

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

144

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20126
        • Recruiting
        • University of Milano-Bicocca
        • Contact:
      • Palermo, Italy, 90127
        • Recruiting
        • Irccs Ismett
        • Contact:
      • Palermo, Italy, 90127
      • Pavia, Italy, 27100
        • Recruiting
        • Istituti Clinici Scientifici Maugeri Spa Società Benefit
        • Contact:
        • Contact:
        • Principal Investigator:
          • Nicola Canessa

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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
  • Stable pain levels and willingness not to modify any ongoing pain management therapies during the study period (1 week)

Exclusion Criteria:

  • History of seizure disorders
  • Active malignancy
  • Implanted medical devices and/or metallic implants in the head or neck region
  • Cranial abnormalities
  • Severe cognitive impairment (Montreal Cognitive Assessment (MoCA)<15.5)
  • Neurological or psychiatric conditions, or significant comorbidities, that may interfere with tDCS
  • Pregnancy
  • Incompatibility with MRI and/or TMS

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Cathodal
Cathodal HD-tDCS
Device: Cathodal High-Definition transcranial Direct Current Stimulation

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.
Active Comparator: Anodal
Anodal HD-tDCS
Device: Anodal High-Definition transcranial Direct Current Stimulation

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.
Sham Comparator: Sham
Sham HD-tDCS
Device: Sham (No Treatment)
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reduction of perceived pain
Time Frame: Baseline; Up to 3 weeks; After 3 months
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in pain-related neural sensitivity measured with fMRI and TMS-EEG
Time Frame: Baseline; Up to 3 weeks
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.
Baseline; Up to 3 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituti Clinici Scientifici Maugeri SpA

Collaborators

University of Palermo
University of Milano Bicocca
IRCCS ISMETT Palermo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 3, 2025

Primary Completion (Estimated)

February 28, 2027

Study Completion (Estimated)

May 31, 2027

Study Registration Dates

First Submitted

January 20, 2026

First Submitted That Met QC Criteria

February 24, 2026

First Posted (Actual)

February 25, 2026

Study Record Updates

Last Update Posted (Actual)

February 25, 2026

Last Update Submitted That Met QC Criteria

February 24, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 37813/2024
  • PNRR-MCNT2-2023-12378259 (Other Grant/Funding Number: Italian Ministry of Health)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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