Transcranial Electrical Stimulation for Comorbid Depression and Chronic Pain

NCT07334561 | Recruiting

• 1 other identifier: 2025-80
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to learn if active transcranial alternating current stimulation (tACS) and transcranial direct current stimulation (tDCS) can improve pain symptoms in patients with major depressive disorder (MDD) and chronic pain symptoms. It will also explore the neural mechanisms underlying these potential effects. The main questions it aims to answer are:

1. 1.Are there any differences in the overall efficacy among the three intervention groups (tACS, tDCS, and sham)?
2. 2.Is active tACS superior to sham stimulation in reducing pain symptoms in patients with MDD and chronic pain over the 2-week treatment period and at the 6-week follow-up?
3. 3.Is active tACS superior to active tDCS in reducing pain symptoms?
4. 4.Does active tACS, compared to tDCS, demonstrate a more persistent improvement in pain symptoms, as measured at the 6-week follow-up?
5. 5.As an exploratory objective, what neural oscillation entrainment mechanisms underlie the potential analgesic effects of tACS?
6. 6.Receive 40 minutes of stimulation (tACS, tDCS, or sham) once daily, 5 days per week, for 2 weeks (10 sessions total).
7. 7.Complete clinical assessments and cognitive tests at baseline, mid-intervention (week 1), post-intervention (week 2), and at a 6-week follow-up.
8. 8.Undergo resting-state functional MRI (rs-fMRI) and blood sample collection at baseline and post-intervention for exploratory biomarker analyses.
9. 9.Receive active tACS (1 mA, 10 Hz, 40 minutes) once daily, 5 days per week, for 2 weeks (10 sessions total), while performing a cognitive task during stimulation.
10. 10.Complete resting-state and task-state EEG recordings at the following time points:

Conditions

Depression Disorder; Chronic Pain

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Achieving MCID on BPI Pain Intensity Subscale

  Description: The BPI is a validated self-administered questionnaire that assesses the severity of pain and its impact on daily functioning. The pain intensity subscale consists of four items rating pain at its "worst," "least," "average," and "current" (right now). Each item is rated on a 0 to 10 numeric rating scale. Higher scores mean a worse outcome. The Minimal Clinically Important Difference (MCID) is defined as a reduction of ≥ 1 point from baseline in the BPI pain intensity score. The outcome is the proportion of participants in each group who achieve this MCID threshold at each follow-up time point.

  At 1 week (mid-intervention), 2 weeks (end of intervention), and 6 weeks (follow-up) post-baseline

Secondary Outcomes (6)

• Percentage Reduction from Baseline in HAMD-17 Total Score

  At 1 week (mid-intervention), 2 weeks (end of intervention), and 6 weeks (follow-up) post-baseline

• Change from Baseline in HAMD-17 Total Score

  At 1 week (mid-intervention), 2 weeks (post-intervention), and 6 weeks (follow-up)

• Change from Baseline in Pain Catastrophizing Scale (PCS) Total Score

  At 1 week (mid-intervention), 2 weeks (end of intervention), and 6 weeks (follow-up) post-baseline

• Change from Baseline in Generalized Anxiety Disorder Scale-7 (GAD-7) Total Score

  At 1 week (mid-intervention), 2 weeks (end of intervention), and 6 weeks (follow-up) post-baseline

• Change from Baseline in Clinical Global Impression (CGI) Total Score

  At 1 week (mid-intervention), 2 weeks (post-intervention), and 6 weeks (follow-up)

Other Outcomes (7)

• Change from Baseline in Brain-Derived Exosome Metabolite Levels

  From baseline to post-intervention at 2 weeks

• Change from Baseline in BPI Pain Intensity Score in the Exploratory Open-Label Cohort

  From baseline to post-intervention at 2 weeks

• Change from Baseline in HAMD-17 Total Score in the Exploratory Open-Label Cohort

  From baseline to post-intervention at 2 weeks

Study Arms (4)

tDCS

EXPERIMENTAL

Participants receive active tDCS. The anodal electrode is placed over the left dorsolateral prefrontal cortex (F3), and the cathodal electrode is placed over the right dorsolateral prefrontal cortex (F4). A constant current of 2 mA is applied for 40 minutes per session, with a 30-second ramp-up and ramp-down period. The intervention is administered once daily for 2 weeks (total of 10 sessions).

Device: tDCS

alpha-tACS

EXPERIMENTAL

Participants receive active alpha-tACS. Two electrodes are placed over F3 and F4. A sinusoidal alternating current at 10 Hz frequency (alpha band) is applied 1 mA (zero-to-peak) at the F3 and F4 electrodes. Stimulation duration is 40 minutes per session, including 30-second ramp-up and ramp-down periods. The intervention is administered once daily, 5 days per week, for 2 weeks (total of 10 sessions).

Device: alpha-tACS

Sham

SHAM COMPARATOR

Sham group using the same electrode montage at F3/F4. To maintain blinding, the stimulator delivers current only during the initial 30-second ramp-up period, followed by an immediate ramp-down, and a final 30-second ramp-up at the end of the stimulation session. This mimics the initial sensation of active stimulation without delivering sufficient current to induce neural modulation.

Device: Sham

Exploratory Open-Label tACS Group

EXPERIMENTAL

Participants in this exploratory arm receive the same active tACS intervention as Arm alpha-tACS, with identical stimulation parameters (e.g., 1 mA, 40 minutes, 10 Hz, targeting the bilateral dorsolateral prefrontal cortex (DLPFC)). This arm is open-label (unblinded): participants and study personnel are aware of the treatment assignment. It serves as a supplementary exploratory cohort to explore preliminary neural oscillation entrainment effects of tACS. Unlike Arms 1-3, this arm is neither randomized nor blinded. Data from this arm will be analyzed separately and are not included in the primary confirmatory hypothesis testing of the randomized controlled trial. The overall study remains double-blind for the three-arm RCT component, with this exploratory arm conducted as an ancillary cohort.

Device: alpha-tACS

Interventions

alpha-tACS DEVICE

Participants receive active alpha-tACS. Two electrodes are placed over F3 and F4. A sinusoidal alternating current at 10 Hz frequency (alpha band) is applied 1 mA (zero-to-peak) at the F3 and F4 electrodes. Stimulation duration is 40 minutes per session, including 30-second ramp-up and ramp-down periods. The intervention is administered once daily, 5 days per week, for 2 weeks (total of 10 sessions).

Exploratory Open-Label tACS Group; alpha-tACS

Sham DEVICE

Sham group using the same electrode montage at F3/F4. To maintain blinding, the stimulator delivers current only during the initial 30-second ramp-up period, followed by an immediate ramp-down, and a final 30-second ramp-up at the end of the stimulation session. This mimics the initial sensation of active stimulation without delivering sufficient current to induce neural modulation.

Sham

tDCS DEVICE

Participants receive active tDCS. The anodal electrode (5 × 5 cm) is placed over the left dorsolateral prefrontal cortex (F3), and the cathodal electrode (5 × 7 cm) is placed over the right dorsolateral prefrontal cortex (F4). A constant current of 2 mA is applied for 40 minutes per session, with a 30-second ramp-up and ramp-down period. The intervention is administered once daily for 2 weeks (total of 10 sessions).

tDCS

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meets the diagnostic criteria for a depressive episode (DSM-5);
• HAMD-17 score of ≥8 and ≤23 (mild-to-moderate depressive symptoms) based on the current assessment;
• or higher on Item 5 of the Brief Pain Inventory (BPI), and persistent pain lasting more than three months;
• Ages 18-80;
• Right-handed, with normal hearing, vision, or corrected vision;
• Have a high school education or higher and be able to understand and complete research-related assessments;
• Maintain a consistent regimen of analgesic and antidepressant medications and psychotherapy (including dosage and type of medication or treatment method) for four weeks prior to enrollment;
• The subject (or his or her legal representative, if applicable) signed an informed consent form stating that he or she understood the purpose and procedure of the trial and was willing to participate in it.

You may not qualify if:

• Diagnosed according to the DSM-5 as meeting any of the following criteria: ① Major depressive disorder or treatment-resistant depression (HAMD-17 score ≥ 24, and the current episode has lasted ≥ 2 years, or the current episode has been unresponsive to treatment with ≥ 2 antidepressants); ② Schizophrenia spectrum disorder; ③ Bipolar I disorder; ④ Anxiety disorders (including generalized anxiety disorder, panic disorder, social anxiety disorder, etc.); ⑤ Depressive disorder caused by a medical condition.
• Experiencing malignant pain caused by cancer pain syndrome, visceral pain (such as stomach pain), referred pain (such as back pain caused by pancreatitis), and so on;
• Patients with severe or unstable physical illnesses, including but not limited to: neurological disorders (such as epilepsy, stroke, migraine, history of cranial surgery, etc.); neurological disorders accompanied by structural brain abnormalities (e.g., traumatic brain injury, recent stroke, brain tumor); cardiovascular diseases (e.g., uncontrolled hypertension, heart failure, arrhythmias, myocardial infarction, etc.); respiratory diseases (e.g., severe sleep apnea syndrome); malignant tumors or immunodeficiency; uncontrolled diabetes (fasting blood glucose \> 12 mmol/L);
• Excessive alcohol consumption within 30 days prior to the start of the trial, or a history of alcohol or drug dependence within the past 6 months;
• Women who are pregnant, breastfeeding, or planning to become pregnant within 3 months of the start of the trial;
• Currently taking medications that affect cortical excitability (e.g., benzodiazepines, antiepileptic drugs);
• Have undergone neurostimulation therapy within the past 3 months, including electroconvulsive therapy (MECT), repetitive transcranial magnetic stimulation (rTMS), or transcranial electrical stimulation (tES);
• Suffers from claustrophobia and is unable to undergo an fMRI scan (applies to subjects who require a functional MRI scan);
• Contraindications to transcranial electrical stimulation (such as intracranial metal implants, pacemakers, cochlear implants, skin abrasions at the stimulation site, or a personal or family history of epilepsy, etc.);
• Currently participating in another clinical trial, has participated in a clinical trial within the past 90 days, or plans to participate in another clinical trial during the study;
• Participants with obvious suicidal tendencies, impulsive behavior, or an inability to cooperate with study evaluators;
• Accompanied by psychotic symptoms;
• Researchers believe there are other circumstances that make a participant unsuitable for the trial;
• Patients with severe cognitive impairment (MMSE ≤ 17) were excluded;
• Participants who are unable to cooperate with the study;

Sponsors & Collaborators

• Shanghai Mental Health Center: lead
• Shanghai 10th People's Hospital: collaborator
• Shanghai Tongji Hospital, Tongji University School of Medicine: collaborator

Study Sites (2)

Shanghai Mental Health Center

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

Shanghai Tenth People's Hospital

Shanghai, Shanghai Municipality, 200072, China

RECRUITING

MeSH Terms

Conditions

Chronic Pain

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Central Study Contacts

Jianhua Chen

CONTACT

(+86) 18017311011; jianhua.chen@smhc.org.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2026
• First Posted: January 12, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: September 4, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

CN (2)