Ignite Creation Date:
2026-03-26 @ 3:14 PM
Ignite Modification Date:
2026-03-30 @ 3:25 AM
Study NCT ID:
NCT07334561
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-16
First Post:
2026-01-03
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Transcranial Electrical Stimulation for Comorbid Depression and Chronic Pain
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D059350', 'term': 'Chronic Pain'}], 'ancestors': [{'id': 'D010146', 'term': 'Pain'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 240}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-05', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-12', 'completionDateStruct': {'date': '2027-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-03-12', 'studyFirstSubmitDate': '2026-01-03', 'studyFirstSubmitQcDate': '2026-01-03', 'lastUpdatePostDateStruct': {'date': '2026-03-16', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-01-12', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Brief Pain Inventory (BPI) - Pain Intensity Subscale', 'timeFrame': 'Baseline, 1 week, 2 weeks, 6 weeks', 'description': 'Description:\n\nThe 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.\n\nThe 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.'}], 'secondaryOutcomes': [{'measure': 'Hamilton Depression Rating Scale-17 (HAMD-17) - Mean Percentage Reduction from Baseline', 'timeFrame': 'Baseline, 1 week, 2 weeks, 6 weeks', 'description': 'The HAMD-17 is a 17-item clinician-rated scale assessing depression severity. Items are rated on 3- or 5-point scales, with total scores ranging from 0 to 52. Higher scores mean a worse outcome (greater depression severity).\n\nThe outcome is the percentage reduction in HAMD-17 total score from baseline at each follow-up time point, calculated using the formula:\n\n\\[(Baseline score - Follow-up score) / Baseline score\\] × 100%\n\nA positive percentage indicates improvement (reduction in depressive symptoms).'}, {'measure': 'Quantitative Sensory Testing (QST) - Change from Baseline', 'timeFrame': 'Baseline, 2 weeks', 'description': 'QST is a standardized psychophysical method used to assess somatosensory function, including pain perception. The testing battery includes thermal (cold and warm detection thresholds, cold and heat pain thresholds) and mechanical (mechanical detection threshold, mechanical pain threshold, wind-up ratio) modalities, following the protocol of the German Research Network on Neuropathic Pain (DFNS).\n\nFor each QST parameter, the change from baseline is calculated as: Follow-up value - Baseline value. The interpretation of higher or lower scores depends on the specific parameter (e.g., increased pain thresholds indicate reduced pain sensitivity, which is a better outcome; decreased mechanical detection thresholds may indicate improved sensory function).'}, {'measure': 'Pain Catastrophizing Scale (PCS) - Mean Percentage Reduction from Baseline', 'timeFrame': 'Baseline, 1 week, 2 weeks, 6 weeks', 'description': 'The PCS is a 13-item self-report scale (0-52, higher scores = worse outcome) assessing catastrophic thoughts about pain across three domains: rumination, magnification, and helplessness. The outcome is the percentage reduction from baseline: \\[(Baseline - Follow-up)/Baseline\\] × 100%.'}, {'measure': 'Generalized Anxiety Disorder Scale-7 (GAD-7) - Mean Percentage Reduction from Baseline', 'timeFrame': 'Baseline, 1 week, 2 weeks, 6 weeks', 'description': 'The GAD-7 is a 7-item self-report scale (0-21, higher scores = worse outcome) assessing anxiety symptoms over the past two weeks. The outcome is the percentage reduction from baseline: \\[(Baseline - Follow-up)/Baseline\\] × 100%.'}, {'measure': 'Pain Sensitivity Questionnaire (PSQ) - Percentage Reduction from Baseline', 'timeFrame': 'Baseline, 1 week, 2 weeks, 6 weeks', 'description': 'The Pain Sensitivity Questionnaire (PSQ) is a 17-item self-reported scale assessing pain sensitivity to daily life situations. Items are rated from 0 (not painful at all) to 10 (worst pain imaginable), with total scores ranging from 0 to 10 (average score). Higher scores mean a worse outcome (greater pain sensitivity).\n\nThe outcome is the percentage reduction from baseline: \\[(Baseline - Follow-up) / Baseline\\] × 100%. Positive values indicate improvement.'}, {'measure': 'Clinical Global Impression (CGI) - Change from Baseline', 'timeFrame': 'Baseline, 1 week, 2 weeks, 6 weeks', 'description': "The Clinical Global Impression (CGI) scale consists of two clinician-rated subscales assessing overall treatment response:\n\nCGI-Severity (CGI-S): Rates the severity of the patient's illness on a 7-point scale from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Higher scores mean a worse outcome.\n\nCGI-Improvement (CGI-I): Rates the patient's improvement compared to baseline on a 7-point scale from 1 (very much improved) to 7 (very much worse). This subscale is only assessed at post-baseline time points. Lower scores mean a better outcome (greater improvement).\n\nThe outcome is the change from baseline in CGI-S score at each follow-up time point, and the CGI-I score at each post-baseline time point."}, {'measure': 'Mini-Mental State Examination (MMSE) - Change from Baseline', 'timeFrame': 'baseline, 1 week, 2 weeks, 6 weeks', 'description': 'The Mini-Mental State Examination (MMSE) is a clinician-administered screening tool that assesses cognitive function across five domains: orientation, registration, attention and calculation, recall, and language. Total scores range from 0 to 30. Higher scores mean a better outcome (better cognitive function). Scores below 24 are generally considered indicative of cognitive impairment.\n\nThe outcome is the change from baseline in MMSE total score at each follow-up time point, calculated as:\n\nFollow-up score - Baseline score\n\nA positive change indicates improvement in cognitive function.'}, {'measure': 'Change from baseline Blood BDNF at 2 weeks, 6weeks', 'timeFrame': 'Baseline, 2 weeks, 6weeks', 'description': 'BDNF in ng/mL'}, {'measure': 'Change from baseline Blood inflammatory factors at 2 weeks, 6weeks', 'timeFrame': 'Baseline, 2 weeks, 6weeks', 'description': 'Inflammatory factors (IL-1β, IL-6, TNF-α, CRP, IL-2, IL-10, TGF-β) in ng/mL'}, {'measure': 'Change from baseline Blood lipid at 2 weeks, 6weeks', 'timeFrame': 'Baseline, 2 weeks, 6weeks', 'description': 'Blood lipid (Triglyceride, Total Cholesterol, Low-density Lipoprotein, High-density Lipoprotein) in mmol/L'}, {'measure': 'Change from baseline Blood Glucose at 2 weeks, 6 weeks', 'timeFrame': 'Baseline, 2 weeks, 6 weeks', 'description': 'Blood Glucose in mmol/L'}, {'measure': 'Change from baseline fNIRS at 2 weeks and 6 weeks', 'timeFrame': 'Baseline, 2 weeks, 6 weeks', 'description': 'Near-infrared brain function detection'}, {'measure': 'Change from baseline MRI/rsfMRI at 2 weeks and 6weeks', 'timeFrame': 'Baseline, 2 weeks, 6weeks', 'description': 'structural magnetic resonance imaging (sMRI) , resting-state functional magnetic resonance imaging (rs-fMRI)'}, {'measure': 'Change from baseline EEG at 1 week, 2 weeks and 6 weeks', 'timeFrame': 'baseline, 1 week, 2 weeks and 6 weeks', 'description': 'Electroencephalography'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Depression Disorder', 'Chronic Pain']}, 'descriptionModule': {'briefSummary': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Aged 18-65 years;\n2. 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);\n3. Report persistent pain lasting ≥3 months and score ≥4 on item 5 of the Brief Pain Inventory (BPI);\n4. 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;\n5. Right-handed, with normal hearing, vision, or corrected vision;\n6. Able to voluntarily provide written informed consent to participate in the study and willing and capable of complying with all study procedures.\n\nExclusion Criteria:\n\n1. 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.\n2. Active suicidal ideation, defined as a score of 4 on item 3 of the HAMD-17.\n3. 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).\n4. Substance use disorder within the past 3 months.\n5. Experience of malignant pain due to cancer pain syndrome, visceral pain (e.g., gastric pain), or referred pain (e.g., back pain from pancreatitis).\n6. Neurological disorders associated with structural brain abnormalities (e.g., traumatic brain injury, recent stroke, brain tumor).\n7. Having undergone neuromodulation treatments within the past 3 months, including electroconvulsive therapy (MECT), repetitive transcranial magnetic stimulation (rTMS), or transcranial electrical stimulation (tES).\n8. 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).\n9. 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.\n10. Signs of dementia or other severe cognitive impairment (MMSE score \\<24).\n11. 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).\n12. Pregnancy or lactation.\n13. 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.\n14. Any contraindications to magnetic resonance imaging (e.g., metal implants, claustrophobia, respiratory or motor impairments).\n15. Inability to cooperate with study assessments.'}, 'identificationModule': {'nctId': 'NCT07334561', 'briefTitle': 'Transcranial Electrical Stimulation for Comorbid Depression and Chronic Pain', 'organization': {'class': 'OTHER', 'fullName': 'Shanghai Mental Health Center'}, 'officialTitle': 'Transcranial Electrical Stimulation for Comorbid Depression and Pain: From Technological Development to Clinical Translation in a Multicenter Trial', 'orgStudyIdInfo': {'id': '2025-80'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Dual-target a-tDCS UHCDS', 'description': '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).', 'interventionNames': ['Device: Dual-target a-tDCS UHCDS']}, {'type': 'EXPERIMENTAL', 'label': 'Single-target a-tDCS', 'description': '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).', 'interventionNames': ['Device: Single-target a-tDCS']}, {'type': 'EXPERIMENTAL', 'label': '10 Hz alpha-tACS', 'description': '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).', 'interventionNames': ['Device: 10 Hz alpha-tACS']}, {'type': 'SHAM_COMPARATOR', 'label': 'Sham tES', 'description': '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.', 'interventionNames': ['Device: Sham tES']}], 'interventions': [{'name': 'Dual-target a-tDCS UHCDS', 'type': 'DEVICE', 'description': '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).', 'armGroupLabels': ['Dual-target a-tDCS UHCDS']}, {'name': 'Single-target a-tDCS', 'type': 'DEVICE', 'description': '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).', 'armGroupLabels': ['Single-target a-tDCS']}, {'name': '10 Hz alpha-tACS', 'type': 'DEVICE', 'description': '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).', 'armGroupLabels': ['10 Hz alpha-tACS']}, {'name': 'Sham tES', 'type': 'DEVICE', 'description': '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.', 'armGroupLabels': ['Sham tES']}]}, 'contactsLocationsModule': {'locations': [{'zip': '200030', 'city': 'Shanghai', 'state': 'Shanghai Municipality', 'country': 'China', 'contacts': [{'name': 'jianhua Chen', 'role': 'CONTACT', 'email': 'jianhua.chen@smhc.org.cn', 'phone': '(+86) 18017311011'}, {'name': 'haoyun Tang', 'role': 'CONTACT', 'email': 'tanghy0809@163.com', 'phone': '(+86) 18117197217'}], 'facility': 'Shanghai Mental Health Center', 'geoPoint': {'lat': 31.22222, 'lon': 121.45806}}, {'zip': '200072', 'city': 'Shanghai', 'state': 'Shanghai Municipality', 'country': 'China', 'contacts': [{'name': 'enzhao Cong', 'role': 'CONTACT', 'email': 'congenzhao@163.com', 'phone': 'congenzhao@163.com'}], 'facility': "Shanghai Tenth People's Hospital", 'geoPoint': {'lat': 31.22222, 'lon': 121.45806}}], 'centralContacts': [{'name': 'Jianhua Chen', 'role': 'CONTACT', 'email': 'jianhua.chen@smhc.org.cn', 'phone': '(+86) 18017311011'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Shanghai Mental Health Center', 'class': 'OTHER'}, 'collaborators': [{'name': "Shanghai 10th People's Hospital", 'class': 'OTHER'}, {'name': 'Shanghai Tongji Hospital, Tongji University School of Medicine', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}