Transcranial Electrical Stimulation for Comorbid Depression and Chronic Pain

NCT07334561 | Not Yet Recruiting

• 1 other identifier: 2025-80
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 2

Brief Summary

This clinical trial aims to investigate a novel non-pharmacological intervention, transcranial electrical stimulation (tES), for the treatment of comorbid depression and chronic pain. The primary objectives are to optimize neurostimulation parameters through a multicenter randomized controlled design and to elucidate the underlying neural circuit-immune interaction mechanisms of this comorbidity. Participants with comorbid depression and chronic pain will be randomly assigned to receive one of four interventions: (1) anodal tDCS unilateral hemispheric concurrent dual-site stimulation (a-tDCS UHCDS) targeting the left DLPFC and M1; (2) single-target anodal tDCS over the left DLPFC; (3) 40 Hz gamma transcranial alternating current stimulation (tACS); or (4) sham stimulation. The intervention period will last for 2 weeks, followed by a series of post-treatment follow-up assessments. Researchers will compare the changes in depression severity (e.g., assessed by HAMD-17) and pain intensity (e.g., NRS, BPI) across groups to evaluate the efficacy. Secondary outcomes include pain perception, quantitative sensory testing (QST), fMRI, MEG, metabolic markers, neurotransmitter and inflammatory biomarkers. This study aims to provide a precise, individualized therapeutic strategy, reduce reliance on pharmacotherapy, and promote the development of domestic high-end medical devices.

Conditions

Depression Disorder; Chronic Pain

Outcome Measures

Primary Outcomes (1)

• Brief Pain Inventory (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.

  Baseline, 1 week, 2 weeks, 6 weeks

Secondary Outcomes (14)

• Hamilton Depression Rating Scale-17 (HAMD-17) - Mean Percentage Reduction from Baseline

  Baseline, 1 week, 2 weeks, 6 weeks

• Quantitative Sensory Testing (QST) - Change from Baseline

  Baseline, 2 weeks

• Pain Catastrophizing Scale (PCS) - Mean Percentage Reduction from Baseline

  Baseline, 1 week, 2 weeks, 6 weeks

• Generalized Anxiety Disorder Scale-7 (GAD-7) - Mean Percentage Reduction from Baseline

  Baseline, 1 week, 2 weeks, 6 weeks

• Pain Sensitivity Questionnaire (PSQ) - Percentage Reduction from Baseline

  Baseline, 1 week, 2 weeks, 6 weeks

Study Arms (4)

Dual-target a-tDCS UHCDS

EXPERIMENTAL

Participants receive active anodal transcranial direct current stimulation (tDCS) delivered via a unilateral hemispheric concurrent dual-site stimulation (UHCDS) montage. Two anodal electrodes are placed over the left dorsolateral prefrontal cortex (DLPFC, F3) and the left primary motor cortex (M1, C3), with a common cathodal reference electrode placed over the contralateral supraorbital area (Fp2). A constant current of 2 mA is applied for 20 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: Dual-target a-tDCS UHCDS

Single-target a-tDCS

EXPERIMENTAL

Participants receive active single-target anodal transcranial direct current stimulation (tDCS). The anodal electrode is placed over the left dorsolateral prefrontal cortex (DLPFC, F3), and the cathodal electrode is placed over the contralateral supraorbital area (Fp2). A constant current of 2 mA is applied for 20 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: Single-target a-tDCS

10 Hz alpha-tACS

EXPERIMENTAL

Participants receive active 10 Hz transcranial alternating current stimulation (tACS). Three 5 × 5 cm electrodes are placed as follows: target electrode over F3, counter electrode over F4, and reference electrode over Cz. A sinusoidal alternating current at 10 Hz frequency (alpha band) is applied with the following intensity parameters: 1 mA (zero-to-peak) at F3 and F4 electrodes, and 2 mA (zero-to-peak) at the Cz reference electrode. 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: 10 Hz alpha-tACS

Sham tES

SHAM COMPARATOR

Participants receive sham transcranial electrical stimulation (tES) using the same electrode montage as the corresponding active groups. 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. For the tACS sham condition, the 40-minute session includes only the ramp-up/ramp-down sequences at the beginning and end. Participants are randomly assigned to one of the three sham montages (dual-target tDCS, single-target tDCS, or tACS) in parallel with the active groups.

Device: Sham tES

Interventions

Dual-target a-tDCS UHCDS DEVICE

Participants receive active anodal transcranial direct current stimulation (tDCS) delivered via a unilateral hemispheric concurrent dual-site stimulation (UHCDS) montage. Two anodal electrodes (5 × 5 cm) are placed over the left dorsolateral prefrontal cortex (DLPFC, F3) and the left primary motor cortex (M1, C3), with a common cathodal reference electrode (5 × 7 cm) placed over the contralateral supraorbital area (Fp2). A constant current of 2 mA is applied for 20 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).

Dual-target a-tDCS UHCDS

Single-target a-tDCS DEVICE

Participants receive active single-target anodal transcranial direct current stimulation (tDCS). The anodal electrode (5 × 5 cm) is placed over the left dorsolateral prefrontal cortex (DLPFC, F3), and the cathodal electrode (5 × 7 cm) is placed over the contralateral supraorbital area (Fp2). A constant current of 2 mA is applied for 20 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).

Single-target a-tDCS

10 Hz alpha-tACS DEVICE

Participants receive active 10 Hz transcranial alternating current stimulation (tACS). Three 5 × 5 cm electrodes are placed as follows: target electrode over F3, counter electrode over F4, and reference electrode over Cz. A sinusoidal alternating current at 10 Hz frequency (alpha band) is applied with the following intensity parameters: 1 mA (zero-to-peak) at F3 and F4 electrodes, and 2 mA (zero-to-peak) at the Cz reference electrode. 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).

10 Hz alpha-tACS

Sham tES DEVICE

Participants receive sham transcranial electrical stimulation (tES) using the same electrode montage as the corresponding active groups. 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. For the tACS sham condition, the 40-minute session includes only the ramp-up/ramp-down sequences at the beginning and end. Participants are randomly assigned to one of the three sham montages (dual-target tDCS, single-target tDCS, or tACS) in parallel with the active groups.

Sham tES

Eligibility Criteria

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

You may qualify if:

• Aged 18-65 years;
• Meet the diagnostic criteria for a depressive episode according to DSM-5, with current mild-to-moderate depressive symptoms (HAMD-17 score ≥8 and ≤23);
• Report persistent pain lasting ≥3 months and score ≥4 on item 5 of the Brief Pain Inventory (BPI);
• Maintain a stable anti-depression drug and psychological treatment plan (including dosage, drug type, or therapeutic approach) for at least four weeks prior to enrollment;
• Right-handed, with normal hearing, vision, or corrected vision;
• Able to voluntarily provide written informed consent to participate in the study and willing and capable of complying with all study procedures.

You may not qualify if:

• Diagnosed with other psychiatric disorders, including schizophrenia spectrum disorders, bipolar I disorder (due to potential risk of manic episodes and contraindication of lithium or anticonvulsants), primary anxiety disorders, depression associated with severe somatic illness, etc.
• Active suicidal ideation, defined as a score of 4 on item 3 of the HAMD-17.
• Severe or treatment-resistant depression (HAMD-17 score ≥23, with current depressive episode lasting at least 2 years or failure to respond to two or more antidepressant treatments during the current episode).
• Substance use disorder within the past 3 months.
• Experience of malignant pain due to cancer pain syndrome, visceral pain (e.g., gastric pain), or referred pain (e.g., back pain from pancreatitis).
• Neurological disorders associated with structural brain abnormalities (e.g., traumatic brain injury, recent stroke, brain tumor).
• Having undergone neuromodulation treatments within the past 3 months, including electroconvulsive therapy (MECT), repetitive transcranial magnetic stimulation (rTMS), or transcranial electrical stimulation (tES).
• Contraindications to transcranial electrical stimulation (e.g., intracranial metal implants, cardiac pacemaker, cochlear implant, skin lesions at stimulation sites, personal or family history of epilepsy).
• Current or within the past 1 month use of medications affecting central nervous system excitability or pain, such as anticonvulsants, lithium, opioids, nonsteroidal anti-inflammatory drugs, and antipsychotics. Occasional as-needed use of acetaminophen as rescue medication is permitted but must be documented in detail in the study diary.
• Signs of dementia or other severe cognitive impairment (MMSE score \<24).
• Severe or unstable somatic diseases, including but not limited to: neurological disorders (e.g., epilepsy, stroke, migraine, history of cranial surgery); cardiovascular diseases (e.g., uncontrolled hypertension, heart failure, arrhythmia, myocardial infarction); respiratory disorders (e.g., severe sleep apnea syndrome); malignancy or immunocompromised status; uncontrolled diabetes (fasting blood glucose \>12 mmol/L).
• Pregnancy or lactation.
• Concurrent participation in another clinical trial, participation in any clinical trial within the past 90 days, or planned participation in another trial during the study period.
• Any contraindications to magnetic resonance imaging (e.g., metal implants, claustrophobia, respiratory or motor impairments).
• Inability to cooperate with study assessments.

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

Location

Shanghai Tenth People's Hospital

Shanghai, Shanghai Municipality, 200072, China

Location

MeSH Terms

Conditions

Chronic Pain

Condition Hierarchy (Ancestors)

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

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: May 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 16, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

CN (2)