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

Leveraging the Therapeutic Benefits of Transcranial Direct Current Stimulation to Treat Chemotherapy-related Chronic Pain and Psycho-cognitive Comorbidities in Cancer Survivors

The goal of this clinical trial is to learn if transcranial direct current stimulation (tDCS) combined with a working-memory task can treat chronic pain and related emotional and cognitive problems after chemotherapy in adult cancer survivors. tDCS is a non-invasive and painless technique that uses a very weak electrical current, applied through two small electrodes on the head, to modulate the activity of certain brain areas. The main questions it aims to answer are:

• Does tDCS reduce chronic pain intensity after chemotherapy in cancer survivors?
• Does tDCS also reduce anxiety, depression, and cognitive problems, and improve the regulation of cortisol, a stress-related hormone?
• Are the effects on pain, anxiety, depression, cognitive problems, and cortisol sustained when treatment continues with a maintenance phase of up to 2 months?

Researchers will compare real tDCS to sham (placebo) tDCS, a look-alike procedure that does not deliver effective stimulation, to see if real tDCS works to reduce pain and improve these symptoms.

Participants will:

• Receive real or sham tDCS (assigned by chance) in 5 daily sessions over 1 week. Each session lasts 20 minutes: 10 minutes at rest and 10 minutes while doing a working-memory task
• If they did not respond to sham tDCS, be offered 5 additional daily sessions of real tDCS
• If they respond to treatment, continue with real tDCS twice a week for up to 2 months
• Complete assessments of pain, mood, memory, attention, and quality of life before treatment, after each phase, and during and at the end of the maintenance phase
• Collect saliva samples to measure cortisol

Study Overview

• Status: Not yet recruiting
• Conditions: Depression; Chronic Pain; Cognitive Dysfunction; Anxiety; Neuropathic Pain; Cancer Survivors; Chemotherapy-Related Chronic Pain
• Intervention / Treatment: Device: Active tDCS with Sternberg task; Device: Sham tDCS with Sternberg task

Detailed Description

Background and rationale. Chronic pain affects a large proportion of cancer survivors and is often accompanied by anxiety, depression, and cognitive impairment after chemotherapy. Current treatments rely heavily on opioids, which have significant side effects. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has shown analgesic effects in some cancer populations, but evidence in cancer survivors, beyond breast cancer, is scarce. This study evaluates tDCS combined with a working-memory task as an adjuvant treatment for chronic pain after chemotherapy and its associated psycho-cognitive comorbidities, both in the short term (acute phase) and over a maintenance period of up to 2 months.

Study design. This is a randomized, double-blind, sham-controlled, parallel-group clinical trial in the acute phase, followed by an open-label crossover phase for non-responders who received sham, and an open-label maintenance phase with active tDCS for responders. It is conducted at university hospitals in the province of Cádiz, Spain. Participants are randomly assigned to active or sham tDCS using a computer-generated randomization sequence kept by independent personnel. Neither participants nor the staff delivering the intervention know the assigned condition during the acute phase.

Procedures. Phase I (acute, double-blind): participants receive 5 consecutive daily sessions (one week) of active or sham tDCS. Stimulation is delivered with a battery-driven constant-current stimulator (Nurostym tES, CE-marked) through two saline-soaked sponge electrodes, with the anode over the primary motor cortex (C3/C4, 10-20 system, contralateral to the most affected side) and the cathode over the contralateral supraorbital region. Active stimulation consists of 2 mA for 20 minutes, with 30-second ramp-up and ramp-down. In sham stimulation, current is applied only briefly at the beginning and end of the session to mimic the sensation of active stimulation. During each 20-minute session, in both conditions, participants receive stimulation at rest for the first 10 minutes and perform the Sternberg working-memory task during the following 10 minutes. At the end of the acute phase, participants are asked which condition they believe they received, to check the integrity of blinding.

Phase II (open-label crossover): participants who received sham tDCS and did not respond receive 5 additional consecutive daily sessions of active tDCS.

Phase III (maintenance, open-label): participants who respond to treatment, defined as a reduction of at least 2 points in pain intensity on the visual analogue scale (VAS) relative to baseline at the end of the acute phase or the crossover phase, receive two sessions of active tDCS per week for up to 2 months as an add-on to standard care, following the same stimulation and task scheme.

Assessments. Assessments are performed at baseline (T0), after the acute phase (T1), after the crossover phase when applicable (T2), one month into the maintenance phase (T3), and at the end of the maintenance phase (T4). Pain intensity, anxiety, depression, cognitive function, quality of life, and diurnal salivary cortisol are assessed at baseline and reassessed after the acute and crossover phases and during and at the end of maintenance, to determine whether the effects of tDCS are sustained over time. Cortisol is collected at home on two consecutive days and analyzed by commercial immunoassay. Samples are coded, used only for research purposes, and processed in duplicate by the research unit. Safety is monitored continuously during each session and at the scheduled visits, with adverse events recorded in the case report form.

Statistical analysis. Sample size was calculated for an expected between-group difference of 2 points in pain intensity (95% confidence, 80% power), giving 25 participants per group, increased to 60 in total to account for attrition. The main analysis follows the intention-to-treat principle. Groups and time points are compared with ANOVA and MANOVA with post hoc corrections. Regression, mediation, moderation, and path analyses will explore the role of cortisol and of clinical variables, including sex, in the response to tDCS.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rocío Gómez-Molinero, PhD; Phone Number: +34956011240; Email: rocio.gomez@uca.es

Study Locations

• Spain
  • Cadiz
    • Jerez de la Frontera, Cadiz, Spain
      • Jerez de la Frontera University Hospital
      • Contact: Javier Jaén Olasolo; Phone Number: +34 956 002 698; Email: javier.jaen.sspa@juntadeandalucia.es
      • Contact: María A Moreno-Santos; Email: mariaa.moreno.santos.sspa@juntadeandalucia.es
  • Cádiz
    • Cadiz, Cádiz, Spain
      • Puerta del Mar University Hospital
      • Contact: Javier Jaén Olasolo; Phone Number: +34 956 002 698; Email: javier.jaen.sspa@juntadeandalucia.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of breast, prostate, lung, or colorectal cancer.
• Presence of chronic pain related to the cancer or its treatment, with a DN4 score ≥ 4
• Refractory to medical treatment for at least two months.
• Completion of systemic chemotherapy.
• Age ≥ 18 years.
• Ability to read, write, and understand the study questionnaires.

Exclusion Criteria:

• Relevant psychiatric or neurological disorders, such as dementia, psychosis, or epilepsy.
• Concomitant disabling medical conditions.
• Intracranial metallic implants or pacemakers.
• Extensive myocardial ischemia.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active tDCS; 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.	Device: Active tDCS with Sternberg task; 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.; Other Names: tDCS; Nurostym tES
Sham Comparator: Sham tDCS; 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.	Device: Sham tDCS with Sternberg task; 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.; Other Names: Sham tDCS; Sham stimulation; Nurostym tES (sham mode)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pain intensity (Visual Analogue Scale, VAS) after the acute phase	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.	Baseline (T0) and after the acute phase at 1 week (T1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pain intensity (Visual Analogue Scale, VAS) from the end of the acute phase through maintenance	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.	From the end of the acute phase at 1 week (T1) to the end of maintenance at up to 2 months (T4)
Change in pain severity and interference (Brief Pain Inventory, BPI)	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).	Baseline (T0), 1 week (T1), 2 weeks (T2), 1 month of maintenance (T3), and end of maintenance at up to 2 months (T4)
Change in anxiety and depression (Hospital Anxiety and Depression Scale, HADS)	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).	Baseline (T0), 1 week (T1), 2 weeks (T2), 1 month of maintenance (T3), and end of maintenance at up to 2 months (T4)
Change in global cognitive function (Montreal Cognitive Assessment, Spanish version, MoCA-S)	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).	Baseline (T0), 1 week (T1), 2 weeks (T2), 1 month of maintenance (T3), and end of maintenance at up to 2 months (T4)
Change in information processing speed (Symbol Digit Modalities Test, SDMT)	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).	Baseline (T0), 1 week (T1), 2 weeks (T2), 1 month of maintenance (T3), and end of maintenance at up to 2 months (T4)
Change in sustained attention and working memory (Paced Auditory Serial Addition Test, PASAT-3)	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).	Baseline (T0), 1 week (T1), 2 weeks (T2), 1 month of maintenance (T3), and end of maintenance at up to 2 months (T4)
Change in verbal fluency (Controlled Oral Word Association Test, COWAT)	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).	Baseline (T0), 1 week (T1), 2 weeks (T2), 1 month of maintenance (T3), and end of maintenance at up to 2 months (T4)
Change in verbal learning and memory (Rey Auditory Verbal Learning Test, RAVLT)	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).	Baseline (T0), 1 week (T1), 2 weeks (T2), 1 month of maintenance (T3), and end of maintenance at up to 2 months (T4)
Change in quality of life (World Health Organization Quality of Life - Brief Version, WHOQOL-BREF)	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).	Baseline (T0), 1 week (T1), 2 weeks (T2), 1 month of maintenance (T3), and end of maintenance at up to 2 months (T4)
Change in diurnal salivary cortisol	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.	Baseline (T0), 1 week (T1), 2 weeks (T2), 1 month of maintenance (T3), and end of maintenance at up to 2 months (T4)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events related to tDCS	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.	From the first tDCS session to the end of participation (up to approximately 3 months)

Collaborators and Investigators

• Sponsor: Instituto de investigación e innovación biomédica de Cádiz
• Collaborators: ESAME BIOMEDICAL S.L.
• Investigators: Principal Investigator: Rocío Gómez-Molinero, PhD, University of Cadiz

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: October 20, 2026
• First Submitted That Met QC Criteria: October 29, 2026
• First Posted (Actual): November 3, 2026

Study Record Updates

• Last Update Posted (Actual): November 3, 2026
• Last Update Submitted That Met QC Criteria: October 29, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: tDCS; Neuromodulation; Chronic Pain; Transcranial Direct Current Stimulation; Chemotherapy; Salivary Cortisol; Cancer Survivorship; Noninvasive Brain Stimulation; Primary Motor Cortex
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neuromuscular Diseases; Behavioral Symptoms; Peripheral Nervous System Diseases; Neurocognitive Disorders; Cognition Disorders; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Anxiety Disorders; Cognitive Dysfunction; Chronic Pain; Depression; Neuralgia; Therapeutics; Behavioral Disciplines and Activities; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Transcranial Direct Current Stimulation
• Other Study ID Numbers: SICEIA-2026-002563; PID2024-157822OA-I00 (Other Grant/Funding Number: Spanish Ministry of Science, Innovation and Universities (MICIU) / State Research Agency (AEI)); ONCOSTIM-CT-01 (Registry Identifier: Sponsor protocol number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No