Depressive Disorder, MajorNCT07161492
Brain Functional Connectivity Mechanism of Cognitive Flexibility Impairment and rTMS Intervention in Major Depressive Disorder
A study testing Repetitive Transcranial Magnetic Stimulation in people with Depressive Disorder, Major and Cognitive Impairment, run by Second Xiangya Hospital of Central South University at 1 site in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Depressive Disorder, Major, Cognitive Impairment
- What is being tested?
- Repetitive Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 105 participants
- Where
- 1 siteChina
- Study dates
- Jul 2026to Oct 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Meet DSM-5 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 (HAMD17≥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 informed consent, and complete assessments and tests.
- Willing to participate voluntarily and sign written informed consent.
Who cannot join
- Meet DSM-5 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Xiangya Second Hospital of Central South University
Changsha, Hunan, 410011
Jin Liu, 13123392823, liujin975@csu.edu.cn
About this study
Official title: Individualized Dual-Target Repetitive Transcranial Magnetic Stimulation (rTMS) Targeting Left Inferior Parietal Lobule and Right Dorsolateral Prefrontal Cortex Functional Connectivity for Cognitive Flexibility Impairment in Major Depressive Disorder: A Randomized, Double-Blind-Controlled Trial
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.
Read the detailed description
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.
- Conditions
- Depressive Disorder, Major, Cognitive Impairment
- Being tested
- Repetitive Transcranial Magnetic Stimulation
- Medical subject headings
- Depressive Disorder, Major, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive Transcranial Magnetic StimulationDevice
Also called rTMS
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
| Study group | Role | What they receive |
|---|---|---|
| Active Dual-Target rTMS Group | Experimental | 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). Receives: Device: Repetitive Transcranial Magnetic Stimulation |
| Active Single-Target rTMS Group | Active comparator | 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). Receives: Device: Repetitive Transcranial Magnetic Stimulation |
| Sham rTMS Control Group | Sham comparator | 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). Receives: Device: Repetitive Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cognitive Flexibility
Measured: Baseline, immediately post-treatment (Day 10), and at 2-week and 4-week follow-ups
Secondary outcomes (1)
Change in Depressive Symptom Severity
Measured: Baseline, immediately post-treatment (Day 10), and at 2-week and 4-week follow-ups
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2025
- Study startJul 2026 (estimated)
- Primary completionAug 2028 (estimated)
- Study completionOct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Depressive Disorder, MajorStudies of the same condition, open and under way.
- More trials run by Second Xiangya Hospital of Central South UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 105 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Fujian Mental Health Center, Xianyue Hospital, Xiamen
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07161492
- Sponsor's protocol ID
- KYZ20250118
- Status last verified
- Jun 2026
- First submitted
- 30 Aug 2025
- Last updated
- 25 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Chen Y, Liu J, Li Z, Liu B, Ji Y, Ju Y, Fang H, Zheng Q, Wang M, Guo W, Li H, Lu X, Li L. The Tendency of Modified Electroconvulsive Therapy-Related Working Memory and Subjective Memory Deficits in Depression: A Prospective Follow-up Study. J ECT. 2020 Sep;36(3):198-204. doi: 10.1097/YCT.0000000000000668.
PubMed 32118689Liu J, Dong Q, Lu X, Sun J, Zhang L, Wang M, Liu B, Ju Y, Wan P, Guo H, Zhao F, Zhang X, Zhang Y, Li L. Influence of comorbid anxiety symptoms on cognitive deficits in patients with major depressive disorder. J Affect Disord. 2020 Jan 1;260:91-96. doi: 10.1016/j.jad.2019.08.091. Epub 2019 Aug 29.
PubMed 31493645Ju Y, Horien C, Chen W, Guo W, Lu X, Sun J, Dong Q, Liu B, Liu J, Yan D, Wang M, Zhang L, Guo H, Zhao F, Zhang Y, Shen X, Constable RT, Li L. Connectome-based models can predict early symptom improvement in major depressive disorder. J Affect Disord. 2020 Aug 1;273:442-452. doi: 10.1016/j.jad.2020.04.028. Epub 2020 May 11.
PubMed 32560939Wang M, Ju Y, Lu X, Sun J, Dong Q, Liu J, Zhang L, Zhang Y, Zhang S, Wang Z, Liu B, Li L. Longitudinal changes of amplitude of low-frequency fluctuations in MDD patients: A 6-month follow-up resting-state functional magnetic resonance imaging study. J Affect Disord. 2020 Nov 1;276:411-417. doi: 10.1016/j.jad.2020.07.067. Epub 2020 Jul 20.
PubMed 32871671Liu J, Fan Y, Ling-Li Zeng, Liu B, Ju Y, Wang M, Dong Q, Lu X, Sun J, Zhang L, Guo H, Futao Zhao, Weihui Li, Zhang L, Li Z, Liao M, Zhang Y, Hu D, Li L. The neuroprogressive nature of major depressive disorder: evidence from an intrinsic connectome analysis. Transl Psychiatry. 2021 Feb 4;11(1):102. doi: 10.1038/s41398-021-01227-8.
PubMed 33542206Liu J, Ju Y, Fan Y, Liu B, Zeng LL, Wang M, Dong Q, Lu X, Sun J, Zhang L, Guo H, Zhao F, Li W, Zhang L, Li Z, Liao M, Zhang X, Zhang Y, Hu D, Li L. Functional connectivity evidence for state-independent executive function deficits in patients with major depressive disorder. J Affect Disord. 2021 Aug 1;291:76-82. doi: 10.1016/j.jad.2021.04.080. Epub 2021 May 21.
PubMed 34023750Guo W, Liu J, Liu B, Wang M, Dong Q, Lu X, Sun J, Zhang L, Guo H, Zhao F, Li W, Li Z, Liao M, Zhang L, Zhang Y, Ju Y, Li L. Relationship between childhood maltreatment and cognitive function in medication-free patients with major depressive disorder. Eur Arch Psychiatry Clin Neurosci. 2023 Aug;273(5):1073-1083. doi: 10.1007/s00406-022-01458-w. Epub 2022 Jul 29.
PubMed 35902412Ju Y, Wang M, Liu J, Liu B, Yan D, Lu X, Sun J, Dong Q, Zhang L, Guo H, Zhao F, Liao M, Zhang L, Zhang Y, Li L. Modulation of resting-state functional connectivity in default mode network is associated with the long-term treatment outcome in major depressive disorder. Psychol Med. 2023 Oct;53(13):5963-5975. doi: 10.1017/S0033291722002628. Epub 2022 Sep 27.
PubMed 36164996Liu J, Chen Y, Xie X, Liu B, Ju Y, Wang M, Dong Q, Lu X, Sun J, Zhang L, Guo H, Zhao F, Li W, Zhang L, Li Z, Liao M, Li L, Zhang Y. The percentage of cognitive impairment in patients with major depressive disorder over the course of the depression: A longitudinal study. J Affect Disord. 2023 May 15;329:511-518. doi: 10.1016/j.jad.2023.02.133. Epub 2023 Feb 28.
PubMed 36863474Liu J, Zhao X, Wei X, Yan D, Ou W, Liao M, Ji S, Peng Y, Wu S, Wang M, Ju Y, Zhang L, Li Z, Liu B, Li L, Zhang Y. Empirical evidence for the neurocognitive effect of nitrous oxide as an adjunctive therapy in patients with treatment resistant depression: A randomized controlled study. Psychiatry Res. 2023 Aug;326:115326. doi: 10.1016/j.psychres.2023.115326. Epub 2023 Jun 26.
PubMed 37390601Guo W, Liu B, Wei X, Ju Y, Wang M, Dong Q, Lu X, Sun J, Zhang L, Guo H, Zhao F, Li W, Li Z, Liao M, Zhang L, Liu J, Zhang Y, Li L. The longitudinal change pattern of cognitive subtypes in medication-free patients with major depressive disorder: a cluster analysis. Psychiatry Res. 2023 Sep;327:115413. doi: 10.1016/j.psychres.2023.115413. Epub 2023 Aug 12.
PubMed 37579539
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Individualized Dual-Target Repetitive Transcranial Magnetic Stimulation (rTMS) Targeting Left Inferior Parietal Lobule and Right Dorsolateral Prefrontal Cortex Functional Connectivity for Cognitive Flexibility Impairment in Major Depressive Disorder: A Randomized, Double-Blind-Controlled Trial
- ClinicalTrials.gov ID
- NCT07161492
- Acronym / sponsor ID
- KYZ20250118
- Conditions
- Depressive Disorder, Major, Cognitive Impairment
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 105 participants (estimated)
- Lead sponsor
- Second Xiangya Hospital of Central South UniversityUniversity, hospital or other
- Collaborators
- Fujian Mental Health Center, Xianyue Hospital, Xiamen
- Study start
- Jul 2026 (estimated)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Oct 2028 (estimated)
- First posted
- 8 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Active Dual-Target rTMS Group | Experimental | Device: Repetitive Transcranial Magnetic StimulationParticipants 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). |
| Active Single-Target rTMS Group | Active comparator | Device: Repetitive Transcranial Magnetic StimulationParticipants 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). |
| Sham rTMS Control Group | Sham comparator | Device: Repetitive Transcranial Magnetic StimulationParticipants 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). |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Meet DSM-5 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 (HAMD17≥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 informed consent, and complete assessments and tests.
- Willing to participate voluntarily and sign written informed consent.
Key exclusion criteria (7 listed)
- Meet DSM-5 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Repetitive Transcranial Magnetic StimulationAlso: rTMSRepetitive 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 | Device | Active Dual-Target rTMS Group, Active Single-Target rTMS Group, Sham rTMS Control Group |
Primary outcome
Change in Cognitive Flexibility
Time frame: Baseline, immediately post-treatment (Day 10), and at 2-week and 4-week follow-ups
1 secondary outcome
Change in Depressive Symptom Severity
Time frame: Baseline, immediately post-treatment (Day 10), and at 2-week and 4-week follow-ups
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2026.
- Results publication: PubMed 32118689Chen Y, Liu J, Li Z, Liu B, Ji Y, Ju Y, Fang H, Zheng Q, Wang M, Guo W, Li H, Lu X, Li L. The Tendency of Modified Electroconvulsive Therapy-Related Working Memory and Subjective Memory Deficits in Depression: A Prospective Follow-up Study. J ECT. 2020 Sep;36(3):198-204. doi: 10.1097/YCT.0000000000000668.
- Results publication: PubMed 31493645Liu J, Dong Q, Lu X, Sun J, Zhang L, Wang M, Liu B, Ju Y, Wan P, Guo H, Zhao F, Zhang X, Zhang Y, Li L. Influence of comorbid anxiety symptoms on cognitive deficits in patients with major depressive disorder. J Affect Disord. 2020 Jan 1;260:91-96. doi: 10.1016/j.jad.2019.08.091. Epub 2019 Aug 29.
- Results publication: PubMed 32560939Ju Y, Horien C, Chen W, Guo W, Lu X, Sun J, Dong Q, Liu B, Liu J, Yan D, Wang M, Zhang L, Guo H, Zhao F, Zhang Y, Shen X, Constable RT, Li L. Connectome-based models can predict early symptom improvement in major depressive disorder. J Affect Disord. 2020 Aug 1;273:442-452. doi: 10.1016/j.jad.2020.04.028. Epub 2020 May 11.
- Results publication: PubMed 32871671Wang M, Ju Y, Lu X, Sun J, Dong Q, Liu J, Zhang L, Zhang Y, Zhang S, Wang Z, Liu B, Li L. Longitudinal changes of amplitude of low-frequency fluctuations in MDD patients: A 6-month follow-up resting-state functional magnetic resonance imaging study. J Affect Disord. 2020 Nov 1;276:411-417. doi: 10.1016/j.jad.2020.07.067. Epub 2020 Jul 20.
- Results publication: PubMed 33542206Liu J, Fan Y, Ling-Li Zeng, Liu B, Ju Y, Wang M, Dong Q, Lu X, Sun J, Zhang L, Guo H, Futao Zhao, Weihui Li, Zhang L, Li Z, Liao M, Zhang Y, Hu D, Li L. The neuroprogressive nature of major depressive disorder: evidence from an intrinsic connectome analysis. Transl Psychiatry. 2021 Feb 4;11(1):102. doi: 10.1038/s41398-021-01227-8.
- Results publication: PubMed 34023750Liu J, Ju Y, Fan Y, Liu B, Zeng LL, Wang M, Dong Q, Lu X, Sun J, Zhang L, Guo H, Zhao F, Li W, Zhang L, Li Z, Liao M, Zhang X, Zhang Y, Hu D, Li L. Functional connectivity evidence for state-independent executive function deficits in patients with major depressive disorder. J Affect Disord. 2021 Aug 1;291:76-82. doi: 10.1016/j.jad.2021.04.080. Epub 2021 May 21.
- Results publication: PubMed 35902412Guo W, Liu J, Liu B, Wang M, Dong Q, Lu X, Sun J, Zhang L, Guo H, Zhao F, Li W, Li Z, Liao M, Zhang L, Zhang Y, Ju Y, Li L. Relationship between childhood maltreatment and cognitive function in medication-free patients with major depressive disorder. Eur Arch Psychiatry Clin Neurosci. 2023 Aug;273(5):1073-1083. doi: 10.1007/s00406-022-01458-w. Epub 2022 Jul 29.
- Results publication: PubMed 36164996Ju Y, Wang M, Liu J, Liu B, Yan D, Lu X, Sun J, Dong Q, Zhang L, Guo H, Zhao F, Liao M, Zhang L, Zhang Y, Li L. Modulation of resting-state functional connectivity in default mode network is associated with the long-term treatment outcome in major depressive disorder. Psychol Med. 2023 Oct;53(13):5963-5975. doi: 10.1017/S0033291722002628. Epub 2022 Sep 27.
- Results publication: PubMed 36863474Liu J, Chen Y, Xie X, Liu B, Ju Y, Wang M, Dong Q, Lu X, Sun J, Zhang L, Guo H, Zhao F, Li W, Zhang L, Li Z, Liao M, Li L, Zhang Y. The percentage of cognitive impairment in patients with major depressive disorder over the course of the depression: A longitudinal study. J Affect Disord. 2023 May 15;329:511-518. doi: 10.1016/j.jad.2023.02.133. Epub 2023 Feb 28.
- Results publication: PubMed 37390601Liu J, Zhao X, Wei X, Yan D, Ou W, Liao M, Ji S, Peng Y, Wu S, Wang M, Ju Y, Zhang L, Li Z, Liu B, Li L, Zhang Y. Empirical evidence for the neurocognitive effect of nitrous oxide as an adjunctive therapy in patients with treatment resistant depression: A randomized controlled study. Psychiatry Res. 2023 Aug;326:115326. doi: 10.1016/j.psychres.2023.115326. Epub 2023 Jun 26.
- Results publication: PubMed 37579539Guo W, Liu B, Wei X, Ju Y, Wang M, Dong Q, Lu X, Sun J, Zhang L, Guo H, Zhao F, Li W, Li Z, Liao M, Zhang L, Liu J, Zhang Y, Li L. The longitudinal change pattern of cognitive subtypes in medication-free patients with major depressive disorder: a cluster analysis. Psychiatry Res. 2023 Sep;327:115413. doi: 10.1016/j.psychres.2023.115413. Epub 2023 Aug 12.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repetitive Transcranial Magnetic Stimulation in people with Depressive Disorder, Major and Cognitive Impairment, run by Second Xiangya Hospital of Central South University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jin Liu (13123392823, liujin975@csu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cognitive Flexibility (time frame: Baseline, immediately post-treatment (Day 10), and at 2-week and 4-week follow-ups). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07161492, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2026.