Transcranial Direct Current Stimulation for Chemotherapy-Related Chronic Pain in Cancer Survivors (ONCOSTIM)

Phase I (acute, double-blind): 5 consecutive daily sessions of active tDCS (2 mA, 20 minutes, 30-second ramp-up and ramp-down) combined with the Sternberg working-memory task (10 minutes at rest, then 10 minutes performing the task). Responders (at least 2-point reduction on the pain VAS from baseline) continue to Phase III (maintenance, open-label): active tDCS with the same scheme twice a week for up to 2 months.

Nurostym tES stimulator (Neuro Device Group SA, Poland; CE-marked) with two saline-soaked sponge electrodes. Anode over the primary motor cortex (C3/C4, 10-20 system, contralateral to the most affected side), cathode over the contralateral supraorbital region. 2 mA for 20 minutes with 30-second ramp-up and ramp-down. During each session, the first 10 minutes are at rest and the next 10 minutes are while performing the Sternberg working-memory task. Acute phase and crossover: 5 consecutive daily sessions. Maintenance: 2 sessions per week for up to 2 months.

• tDCS
• Nurostym tES

Phase I (acute, double-blind): 5 consecutive daily sessions of sham tDCS (brief ramp-up and ramp-down at the beginning and end of the session, without sustained stimulation) combined with the Sternberg working-memory task (10 minutes at rest, then 10 minutes performing the task). Non-responders then receive Phase II (open-label crossover): 5 consecutive daily sessions of active tDCS. Responders, after Phase I or Phase II, continue to Phase III (maintenance, open-label): active tDCS twice a week for up to 2 months.

Same device, electrode placement, and session schedule as active tDCS, with current delivered only during the 30-second ramp-up and ramp-down at the beginning and end of the session to mimic the sensation of active stimulation, without sustained stimulation. Participants also perform the Sternberg working-memory task (10 minutes at rest, then 10 minutes performing the task). 5 consecutive daily sessions in the acute phase.

• Sham tDCS
• Stimolazione fittizia
• Nurostym tES (sham mode)

Change from baseline in pain intensity measured with the Visual Analogue Scale (VAS), comparing active tDCS with sham tDCS. Scores range from 0 (no pain) to 10 (worst imaginable pain); higher scores indicate a worse outcome. Responders are defined as participants with a reduction of at least 2 points from baseline.

Change in pain intensity measured with the Visual Analogue Scale (VAS), relative to baseline, from the end of the acute phase through the end of maintenance (assessed at T2, T3, and T4). Scores range from 0 (no pain) to 10 (worst imaginable pain); higher scores indicate a worse outcome.

Change from baseline in pain severity and pain interference with daily functioning measured with the Brief Pain Inventory - Short Form (BPI-SF). The severity score (mean of 4 items) and the interference score (mean of 7 items) each range from 0 to 10; higher scores indicate greater severity and interference (worse outcome).

Change from baseline in anxiety and depression symptoms, measured with the 14-item Hospital Anxiety and Depression Scale (HADS). The anxiety and depression subscales each range from 0 to 21; higher scores indicate more severe symptoms (worse outcome).

Change from baseline in global cognitive function, measured with the Spanish version of the Montreal Cognitive Assessment (MoCA-S). Total scores range from 0 to 30; higher scores indicate better cognitive function (better outcome).

Change from baseline in information processing speed and attention measured with the written Symbol Digit Modalities Test (SDMT), scored as the number of correct responses in 90 seconds. Scores range from 0 to 110; higher scores indicate better performance (better outcome).

Change from baseline in sustained and divided attention and working memory measured with the 3-second version of the Paced Auditory Serial Addition Test (PASAT-3), scored as the number of correct responses. Scores range from 0 to 60; higher scores indicate better performance (better outcome).

Change from baseline in executive function and semantic and phonemic verbal fluency measured with the Controlled Oral Word Association Test (COWAT), scored as the total number of correct words generated (60 seconds per letter or category). The minimum score is 0 and there is no fixed maximum; higher scores indicate better performance (better outcome).

Change from baseline in verbal learning and short- and long-term auditory-verbal memory measured with the Rey Auditory Verbal Learning Test (RAVLT). Total learning across trials 1-5 ranges from 0 to 75; immediate (post-interference) and delayed recall each range from 0 to 15; higher scores indicate better performance (better outcome).

Change from baseline in quality of life measured with the 26-item World Health Organization Quality of Life - Brief Version (WHOQOL-BREF). Physical, psychological, social relationships and environment domain scores are transformed to a 0-100 scale; higher scores indicate better quality of life (better outcome).

Change from baseline in diurnal salivary cortisol, measured in saliva samples collected on two consecutive days and analyzed in duplicate by immunoassay. Mean values of the samples taken at the same time of day on both days are used. Concentrations are expressed in nmol/L.

Adverse events (e.g., tingling, stinging, itching, headache, skin redness) actively recorded during each stimulation session and at the scheduled visits, with severity, causality, and outcome documented.