Positron Emission Tomography in Transcranial Magnetic Stimulation Intervention for Treatment-resistant Depression

NCT06044324 | Enrolling By Invitation

• 1 other identifier: IIT20240155C-R1
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Major depressive disorder (MDD) exhibit reduced visual motor perception, which affects prognosis. Metabolic substance changes and abnormal neural activity in the middle temporal visual area (MT) mediate this perceptual dysfunction. The main questions are: •there is no conclusive evidence of impairment of visual motion suppression in treatment-resistant depression (TRD); •it is unknown that functional abnormalities in the MT of TRD patients mediate possible changes in visual perception •lack of treatment for deficit in visual motor perception; •mechanisms behind the intervention process need to be explored. The goal of this clinical trial is to understand the function of visual motor perception in TRD, to validate the effect of the MT on visual motion perception and to explore the effectiveness of the intervention as well as the neurophysiological mechanisms. This study was planned to •explore any differences in visual motor perception and function of MT between TRD and healthy controls; •analyze the influence of neurobiological changes in MT and related brain regions on visual motion perception; •investigate the effects of rTMS intervention in MT for treatment of impaired visual perception function in TRD; •studying potential therapeutic mechanisms by PET/MRI imaging. Participants will divide into TRD group and HC group. Clinical symptoms, scales, visual perception suppression index, PET/MRI, electrophysiology and other clinical data were collected at baseline for both two groups. TRD group received high-frequency rTMS stimulation targeting the MT. Besides, psychological scales, visual suppression index, PET/MRI, electrophysiology and other clinical data were collected during the intervention and after treatment. The researchers will •compare the differences in visual perceptual function and neurobiological characteristics between the TRD group and the HC group in baseline; •analyze the impact of MT and related brain regions in visual motion perception; •compare the suppression index before and after intervention in TRD to discuss the feasibility of rTMS stimulation targeting the MT to improve visual motion perception abnormalities；•utilize the changes in clinical data of PET/MRI and electrophysiology before and after the treatment of TRD group to explore the possible underlying mechanisms during the treatment process.

Conditions

Treatment Resistant Depression; Visual Perceptual Weakness

Keywords

Repetitive Transcranial Magnetic Stimulation; PET/MRI

Outcome Measures

Primary Outcomes (6)

• Change in Suppression Index after treatment

  Suppression Index (SI) defined as the difference of log10 thresholds for large versus small stimuli of gratings, is able to quantify the suppression strength. The higher the numerical value, the more severe the visual motor perception deficit.

  Baseline

• Change in Suppression Index after treatment

  Suppression Index (SI) defined as the difference of log10 thresholds for large versus small stimuli of gratings, is able to quantify the suppression strength. The higher the numerical value, the more severe the visual motor perception deficit.

  2 weeks

• Hamilton Depression Scale (24-items) Total Score Change

  The Hamilton Depression Scale (24-items), is a 24 item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. It's considered the gold standard for rating depression severity and used frequently in clinical trials. Higher HAM-D24 score indicates more severe depression, and each item yields a score of 0 to 4. The higher scores representing more severe levels of depression. Remission is defined as HAM-D24 ≤8. A reduction of 50% or more in total score from Baseline indicates clinical response.

  Baseline

• Hamilton Depression Scale (24-items) Total Score Change

  The Hamilton Depression Scale (24-items), is a 24 item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. It's considered the gold standard for rating depression severity and used frequently in clinical trials. Higher HAM-D24 score indicates more severe depression, and each item yields a score of 0 to 4. The higher scores representing more severe levels of depression. Remission is defined as HAM-D24 ≤8. A reduction of 50% or more in total score from Baseline indicates clinical response.

  2 weeks

• Change in synaptic density using positron emission tomography/magnetic resonance imaging

  Positron emission tomography/magnetic resonance imaging (PET/MRI) is a fusion of PET and MRI, which integrates pathophysiological changes with morphological structure. Research using PET/MRI in major depression has shown that there are alterations in the snyaptic density of certain brain regions in people with the condition and synaptic dysfunction in the dorsolateral prefrontal cortex may have implications for the downstream organization of functional networks. The SV2A radioligand \[11C\]UCB-H can examine snyaptic density in human brain. And brain structure, function connectivity and spectrum of metabolic substances can be measured by MRI. Overall, PET/MRI has advantages for the diagnosis of major depression and the evaluation of treatment effects.

  Baseline

• Change in synaptic density using positron emission tomography/magnetic resonance imaging

  Positron emission tomography/magnetic resonance imaging (PET/MRI) is a fusion of PET and MRI, which integrates pathophysiological changes with morphological structure. Research using PET/MRI in major depression has shown that there are alterations in the snyaptic density of certain brain regions in people with the condition and synaptic dysfunction in the dorsolateral prefrontal cortex may have implications for the downstream organization of functional networks. The SV2A radioligand \[11C\]UCB-H can examine snyaptic density in human brain. And brain structure, function connectivity and spectrum of metabolic substances can be measured by MRI. Overall, PET/MRI has advantages for the diagnosis of major depression and the evaluation of treatment effects.

  2 weeks

Secondary Outcomes (44)

• Change in Suppression Index after treatment

  1 week

• Change in Suppression Index after treatment

  6 weeks

• Change in the score of Visual Analog Scale (VAS)

  Baseline

• Change in the score of Visual Analog Scale (VAS)

  1 week

• Change in the score of Visual Analog Scale (VAS)

  2 weeks

Study Arms (2)

Repetitive Transcranial Magnetic Stimulation

ACTIVE COMPARATOR

Stimulation site: According to the localization of neural orientation navigation system, magnetic resonance data was read in Brainsight software, and three-dimensional brain reconstruction was carried out. The stimulation target was located in the coordinates of Montreal Neurological Institute (MNI), which was located in the left middle temporal (-43, -73, 10). Treatment intensity was 100% exercise threshold, continuous 10Hz stimulation, repeated 75 times, that is, 3000 pulses per treatment, 2 times a day, stimulation lasted for 4 seconds with a 26-second interval for 37.5 minutes, continuous stimulation for 5 days, 2 days rest interval, and 5 days of continuous stimulation.

Device: Repetitive Transcranial Magnetic Stimulation

HC observation

NO INTERVENTION

Collect data on healthy controls without stimulation. The subjects get clinical evaluation, blood sample collection, positron emission tomography-magnetic resonance scanning, and electrophysiological monitoring.

Interventions

Repetitive Transcranial Magnetic Stimulation DEVICE

Participants in the active stimulation group will receive the high frequency rTMS to left middle temporal visual area. The left middle temporal visual area will be targeted utilizing the neuronavigation system. Stimulation intensity will be standardized at 100% of RMT. Stimulation will be delivered to the left middle temporal visual area using an NTK-TMS-II100 TMS device,is compatible with the Brainsight TMS navigation system.

Repetitive Transcranial Magnetic Stimulation

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Receive two or more adequate doses and courses of antidepressant drugs in different mechanisms that were not effective and had been stable for more than 6 weeks on antidepressant medication prior to enrollment, with non-responsiveness defined as a decrease in HAMD-24 score of \<50%.
• item Hamilton Depression Scale (HAMD-24) ≥ 20.
• Normal or corrected to normal vision.
• Ability to complete spatial suppression psychophysical experiment.
• education background above the college degree.
• Age 18-45 years, regardless of gender.
• Right-handedness.
• Han Chinese.
• Signed a written informed consent, willing to participate in the study and be evaluated.

You may not qualify if:

• Co-morbid other mental disorders, including: schizophrenia, mental retardation, substance dependence, etc.
• Patients with metal objects in the body or with other contraindications to PET-MRI scanning
• Patients with severe or unstable somatic diseases
• Women during pregnancy or lactation, and women of childbearing age with positive urine HCG test results during the screening period
• Benzodiazepines were taken during the experimental period
• Other conditions that, in the opinion of the investigator, exist that make participation in this clinical trial inappropriate.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (1)

The First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, 310000, China

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2023
• First Posted: September 21, 2023
• Study Start: November 1, 2023
• Primary Completion: December 1, 2025
• Study Completion: May 1, 2026
• Last Updated: March 18, 2025

Record last verified: 2024-10

Locations

CN (1)