Ignite Creation Date:
2025-12-24 @ 3:30 PM
Ignite Modification Date:
2025-12-29 @ 10:05 AM
Study NCT ID:
NCT07161492
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-09-08
First Post:
2025-08-30
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Study on Functional Connectome and rTMS Intervention of Cognitive Flexibility Impairment in Patients With Major Depressive Disorder
Sponsor:
Second Xiangya Hospital of Central South University
Organization:
Study Overview
Official Title:
Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cognitive Flexibility and Brain Functional Connectivity in Patients With Major Depressive Disorder: A Randomized Controlled Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2025-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Persistent cognitive impairment in major depressive disorder (MDD) affects both treatment outcomes and psychosocial functioning, emphasizing the critical need for effective treatment. However, there is still a lack of effective treatment at present. Our previous studies found that the impairment in cognitive flexibility (CF) persisted even in remitted patients with MDD. This impairment was correlated with hypo-connectivity between the left inferior parietal lobule (IPL) and the right dorsal prefrontal cortex (dPFC). Based on these findings, we hypothesize that the hypo-connectivity between the left IPL and the right dPFC is the neural basis of CF impairment, and targeted interventions of this connection may alleviate CF impairment and thus improve treatment outcomes as well as psychosocial functioning of patients with MDD. The present study proposes to employ cognitive training for MDD patients with CF impairment. By comparing changes in CF and brain functional connectivity via task-based fMRI before and after the intervention, we aim to clarify the effect of cognitive training on cognitive performance, treatment outcomes and psychosocial functioning, and identify the critical role of the hypo-connectivity between the left IPL and the right dPFC underlying CF impairment. Furthermore, we will conduct a randomized controlled trial to investigate the effect of individualized dual-target repetitive transcranial magnetic stimulation (rTMS) on CF by targeting the hypo connectivity between the left IPL and the right dPFC. The results will further validate the critical role of this connection in modulating CF performance and provide a reliable intervention target for reducing CF impairment.
Detailed Description:
This is a mechanistic clinical trial investigating the neural basis of cognitive flexibility (CF) impairment in major depressive disorder (MDD) and the therapeutic effects of targeted neuromodulation. The study consists of three integrated components:
1. Component 1 (RCT: CCRT vs. TAU)
MDD patients with CF impairment will be randomized to:
* Arm A: Computerized Cognitive Remediation Therapy (CCRT) targeting CF + Treatment As Usual (TAU)
* Arm B: TAU alone Objective : Examine whether CCRT improves CF and whether CF improvement translates to better clinical/functional outcomes.
2. Component 2 (Neuroimaging Biomarker Study)
Cross-sectional comparison of:
* CF-impaired MDD patients
* CF-intact MDD patients Objective : Identify functional connectivity (FC) signatures of CF impairment using task-based fMRI during cognitive flexibility tasks.
3. Component 3 (RCT: Active vs. Sham rTMS)
CF-impaired MDD patients will be randomized to:
* Arm C: Individualized dual-target rTMS (left IPL-right dPFC) + TAU
* Arm D: Sham rTMS + TAU Objective : Test whether cc-PAS rTMS normalizes left IPL-right dPFC hypo-connectivity and improves CF.
Scientific Rationale :
Hypo-connectivity between left inferior parietal lobule (IPL) and right dorsal prefrontal cortex (dPFC) is hypothesized to be a key neural mechanism underlying persistent CF impairment in MDD. This study aims to:
* Validate this circuit as a therapeutic target
* Establish fMRI-guided cc-PAS rTMS as a precision intervention
Methodology :
Individualized targeting : fMRI-guided neuronavigation (Dolphin Robotics) to identify subject-specific IPL/dPFC coordinates Novel stimulation : Cortico-cortical paired associative stimulation (cc-PAS) to modulate directional connectivity Cognitive phenotyping : Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT-B/A) as primary CF measures
1. Component 1 (RCT: CCRT vs. TAU)
MDD patients with CF impairment will be randomized to:
* Arm A: Computerized Cognitive Remediation Therapy (CCRT) targeting CF + Treatment As Usual (TAU)
* Arm B: TAU alone Objective : Examine whether CCRT improves CF and whether CF improvement translates to better clinical/functional outcomes.
2. Component 2 (Neuroimaging Biomarker Study)
Cross-sectional comparison of:
* CF-impaired MDD patients
* CF-intact MDD patients Objective : Identify functional connectivity (FC) signatures of CF impairment using task-based fMRI during cognitive flexibility tasks.
3. Component 3 (RCT: Active vs. Sham rTMS)
CF-impaired MDD patients will be randomized to:
* Arm C: Individualized dual-target rTMS (left IPL-right dPFC) + TAU
* Arm D: Sham rTMS + TAU Objective : Test whether cc-PAS rTMS normalizes left IPL-right dPFC hypo-connectivity and improves CF.
Scientific Rationale :
Hypo-connectivity between left inferior parietal lobule (IPL) and right dorsal prefrontal cortex (dPFC) is hypothesized to be a key neural mechanism underlying persistent CF impairment in MDD. This study aims to:
* Validate this circuit as a therapeutic target
* Establish fMRI-guided cc-PAS rTMS as a precision intervention
Methodology :
Individualized targeting : fMRI-guided neuronavigation (Dolphin Robotics) to identify subject-specific IPL/dPFC coordinates Novel stimulation : Cortico-cortical paired associative stimulation (cc-PAS) to modulate directional connectivity Cognitive phenotyping : Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT-B/A) as primary CF measures
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: