An interventional study of Repetitive Transcranial Magnetic Stimulation in Depressive Disorder, Major and Cognitive Impairment, sponsored by Second Xiangya Hospital of Central South University. Not yet recruiting at 1 site in China. Open to participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2026-06-25.
Sponsored by Second Xiangya Hospital of Central South University · Not applicable, Interventional, and Treatment
Major depressive disorder (MDD) often involves cognitive deficits, particularly in cognitive flexibility, which is inadequately addressed by standard antidepressants. This study tests an innovative brain stimulation regimen: individualized dual-target repetitive transcranial magnetic stimulation (rTMS) to improve cognitive flexibility in MDD patients.
This is a randomized, double-blind, sham-controlled trial that plans to enroll 105 MDD patients with cognitive flexibility impairment. Participants will be randomly assigned to one of three groups: (1) Active dual-target group - receiving active rTMS over both the left inferior parietal lobule (IPL) and the right dorsolateral prefrontal cortex (DLPFC); (2) Active single-target group - receiving active rTMS over the left IPL and sham stimulation over the right DLPFC; (3) Sham control group - receiving sham stimulation over both targets. All participants will continue their stable antidepressant medication (SSRI or SNRI). The rTMS intervention lasts 10 days, with 5 stimulation sessions per day.
Cognitive flexibility, depressive symptoms, and brain functional connectivity will be assessed at baseline, immediately after the 10-day treatment, and at 2-week and 4-week follow-ups using neurocognitive tests, clinical rating scales (e.g., HAMD), and functional MRI. The results will help confirm the role of the IPL-DLPFC connectivity in cognitive flexibility and may establish a new treatment target for cognitive dysfunction in MDD.
Major depressive disorder (MDD) is a highly prevalent and recurrent chronic psychiatric illness. Over 50% of patients in the acute phase show widespread and significant cognitive impairments affecting executive function, attention, processing speed, and memory. Among executive subdomains, cognitive flexibility - the capacity to adapt thoughts and behaviors to changing environmental demands - is particularly difficult to treat. Even after 6 months of antidepressant treatment, cognitive flexibility often fails to return to healthy levels, and its impairment worsens with recurrent episodes and longer illness duration.
Functional MRI (fMRI) evidence points to the inferior parietal lobule (IPL) as a key node activated during cognitive flexibility tasks, while the dorsolateral prefrontal cortex (DLPFC) mediates top-down cognitive control. We therefore hypothesize that decreased functional connectivity between the left IPL and right DLPFC is the critical neural basis for cognitive flexibility impairment in MDD, and that targeted modulation of this connection can improve flexibility.
Study Design
This is a randomized, double-blind, sham-controlled, multi-center trial. A total of 105 MDD patients with cognitive flexibility impairment will be enrolled and allocated 1:1:1 to:
Active dual-target group (n=35): active rTMS over left IPL + active rTMS over right DLPFC; Active single-target group (n=35): active rTMS over left IPL + sham over right DLPFC; Sham control group (n=35): sham rTMS over both targets. All participants will continue their stable SSRI or SNRI treatment as usual (TAU). rTMS will be delivered using MRI-guided neuronavigation for individualized target localization. The stimulation regimen consists of 5 paired sessions per day (with a 50-minute inter-session interval) for 10 consecutive days.
Outcomes and Follow-up
Assessments will occur at baseline, immediately post-treatment (Day 10), and at 2-week and 4-week post-treatment:
Primary outcome: cognitive flexibility, measured by the Trail Making Test difference score (TMT-B minus TMT-A) and by task-switching behavioral performance.
Secondary outcomes: depressive symptom severity (HAMD), anxiety (HAMA, ), functional disability (Sheehan Disability Scale, SDS), suicidal ideation (Beck Suicidal Ideation scale, BSI), and other clinical measures.
Imaging: structural, resting-state acquired on a Siemens 3.0T MRI scanner to assess IPL-DLPFC functional connectivity changes.
Safety: adverse events, vital signs, and pain rating (Visual Analogue Scale, VAS).
Significance This study may identify the key functional connectivity basis of cognitive flexibility impairment in MDD and provide a novel, individually-targeted rTMS strategy. If effective, it will offer new evidence for treating cognitive dysfunction in depression and establish a clinically actionable brain network target.
3,041 studies on the registry are indexed under Depressive Disorder, Major; 588 are open to participants now.
This study's planned enrollment of 105 is above the median of 79 across 2,530 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →Second Xiangya Hospital of Central South University is the lead sponsor of 87 studies on the registry; 50 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Meet criteria for major depressive episode confirmed by the Structured Clinical Interview for DSM-5 Disorders (SCID-5), with no prior manic or hypomanic episodes; diagnosed as major depressive disorder without psychotic features by two attending psychiatrists.
First episode or recurrent, currently in a depressive episode (HAMD_17≥17).
Age 18 to 45 years, all sexes and genders. Han Chinese, right-handed. Junior high school education or above, no color blindness, able to understand and provide , and complete assessments and tests.
Willing to participate voluntarily and sign written informed consent.
Exclusion Criteria:
Meet diagnostic criteria for any psychiatric disorder other than major depressive disorder.
Received non-pharmacological treatments within the past 6 months, such as electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), or systematic psychotherapy (≥ 10 sessions).
Prior treatment with CCRT. Received antipsychotics or other medications affecting cognitive function within the past month, or cholinergic agents (e.g., donepezil, galantamine) within 14 days, memantine within 20 days, or other racetam drugs (e.g., piracetam) within 2 days prior to randomization.
Organic brain disorders or severe physical illnesses (e.g., thyroid disease, lupus erythematosus, diabetes, liver/kidney/lung impairment, infection, major trauma).
History of traumatic brain injury with loss of consciousness or other conditions that may interfere with this study.
History of alcohol or substance abuse or dependence. Severe suicidal ideation or suicide attempt . Currently receiving hormonal therapy. Pregnancy, lactation, possibility of pregnancy, or planned pregnancy. History of epilepsy or family history of epilepsy. Implanted metal materials in the body (e.g., pacemaker, dental implants, metal intrauterine device).
Any other factors that, in the investigator's opinion, place the participant at potential risk or interfere with the study participation.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants receive active repetitive transcranial magnetic stimulation (rTMS) over both the left inferior parietal lobule (IPL) and the right dorsolateral prefrontal cortex (DLPFC) using MRI-guided neuronavigation. Stimulation is delivered in 5 paired sessions per day (with a 50-minute inter-session interval) for 10 consecutive days. All participants continue stable SSRI or SNRI antidepressant treatment as usual (TAU).
Device: Repetitive Transcranial Magnetic Stimulation
Participants receive active rTMS over the left inferior parietal lobule (IPL) and sham stimulation over the right dorsolateral prefrontal cortex (DLPFC) using MRI-guided neuronavigation. Stimulation is delivered in 5 paired sessions per day (with a 50-minute inter-session interval) for 10 consecutive days. All participants continue stable SSRI or SNRI antidepressant treatment as usual (TAU).
Device: Repetitive Transcranial Magnetic Stimulation
Participants receive sham rTMS over both the left inferior parietal lobule (IPL) and the right dorsolateral prefrontal cortex (DLPFC) using MRI-guided neuronavigation. Sham stimulation mimics the sensation of active rTMS without delivering magnetic stimulation. Stimulation is delivered in 5 paired sessions per day (with a 50-minute inter-session interval) for 10 consecutive days. All participants continue stable SSRI or SNRI antidepressant treatment as usual (TAU).
Device: Repetitive Transcranial Magnetic Stimulation
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that uses magnetic pulses to modulate neuronal activity in targeted cortical regions. In this study, rTMS is delivered using a commercially available magnetic stimulator with a figure-of-eight coil. Stimulation targets - the left inferior parietal lobule (IPL) and the right dorsolateral prefrontal cortex (DLPFC) - are individually localized using MRI-guided neuronavigation based on each participant's structural magnetic resonance imaging. Each stimulation session consists of paired target stimulation (IPL and DLPFC) with a 50-minute inter-session interval. Treatment is administered as 5 paired sessions per day for 10 consecutive days. Sham stimulation uses the same device and coil placement but delivers no active magnetic stimulation, mimicking the sensory experience of active r
Also known as: rTMS
Change in Cognitive Flexibility
Time frame: Baseline, immediately post-treatment (Day 10), and at 2-week and 4-week follow-ups
Change in Depressive Symptom Severity
Time frame: Baseline, immediately post-treatment (Day 10), and at 2-week and 4-week follow-ups
Plan to share: Undecided
Start is estimated for Jul 2026; primary completion for Aug 2028, 25 months later.
Of 647 non-industry interventional studies with no phase under Depressive Disorder, Major, half reached primary completion within 35 months of starting (the median), counting those still running; a quarter within 19 and three quarters within 55. This study's planned 25 months is below that.
Counting every sponsor, half of 687 studies reached it within 33 months; a quarter within 17 and three quarters within 55.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
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Second Xiangya Hospital of Central South University