Electroencephalography-based Precise Repetitive Transcranial Magnetic Stimulation Treatment

• ClinicalTrials.gov Identifier: NCT06385405
• Recruitment Status: Not yet recruiting
• First Posted: April 26, 2024
• Last Update Posted: May 9, 2024
• Sponsor: Shanghai Mental Health Center
• Collaborators: National Natural Science Foundation of China; Shanghai Municipal Science and Technology Commission; Shanghai Jiao Tong University School of Medicine
• Information provided by (Responsible Party): Tianhong ZHANG, Shanghai Mental Health Center

Study Description

Brief Summary:

This study will focus on the hypothesis that repetitive transcranial magnetic stimulation (TMS) based on EEG personalized modulation may be more effective in promoting symptomatic relief of major depressive disorder (MDD), and will rely on the platform of neuroimaging and function brain imaging of Shanghai Mental Health Center (SMHC), an authoritative institution in the field of mental health. We will eventually facilitate optimization of physical therapy for major depressive disorder (MDD).

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder (MDD)	Device: Individualized alpha frequency Transcranial Magnetic Stimulation (αTMS) Treatment; Device: 10Hz-frequency TMS treatment over the left dorsolateral prefrontal cortex (DLPFC)	Not Applicable

Detailed Description:

Major depression disorder (MDD) is increasingly conceptualized as a disorder of brain networks, which related to dysregulation of functional connectivity. rTMS has the advantages of being safe, non-invasive and well-tolerated, and has been clarified by the FDA to be used in the treatment of depression with some positive efficacy. Machine learning based on EEG data, exploring machine learning and big data analytics methods, and applying the output reference value recommendations to the personalized treatment of depressed patients are expected to be more effective in promoting the alleviation of patients' depressive symptoms.

Every participant meeting the inclusion criteria will be fully informed of the study and be asked to sign the written informed consent before enrollment. Outpatient physicians will conduct the initial screening, collecting all diagnostic and medication information from the medical records at each follow-up visit. Several psychiatrists, all of whom are qualified and well-trained, will conduct clinical assessments at baseline and follow-up at the end of weekly TMS treatments, as well as clinical follow-up 3 months after the end of treatment. Clinical assessments will include HAMD, HAMA, CGI scale and etc. EEG parameter assessments will include changes in alpha-band spectral connectivity at baseline and after every 5 TMS treatments.

During the treatment period, patients will be randomly grouped into the precision group, which will be treated with rTMS based on personalized modulation of EEG data, and the conventional group, which will be treated with TMS at a frequency of 10 Hz to stimulate the left dorsolateral prefrontal cortex (DLPFC). The treatments will be administered once a day, 5 times a week for 4 weeks, totaling 20 sessions. At the end of each week's treatment the patient's EEG will be recorded and the patient will be clinically evaluated by a qualified and well-trained psychiatrist. The original medication regimen will be maintained as much as possible during the treatment period, and adverse effects such as headaches will be faithfully recorded.

According to the sample size calculation formula in the GPower software, a minimum sample size of 64 cases per group is required for this clinical trial. As it is to be expected that due to the complex study protocol with several examinations at a total of four time points, about 15% of the data will be lost, at least 75 patients per group should be recruited. Therefore, the investigators plan to recruit 150 participants. Considering a dropout rate of 15%, 128 cases of MDD will be followed up.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: To test the hypothesis that repetitive transcranial magnetic stimulation based on individualized EEG modulation may be more effective in promoting symptomatic relief of major depressive disorder (MDD), patients were tested in a parallel controlled trial.During the treatment period, patients will be randomly grouped into the precision group, which will be treated with rTMS based on personalized modulation of EEG data, and the conventional group, which will be treated with TMS at a frequency of 10 Hz to stimulate the left dorsolateral prefrontal cortex (DLPFC).
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Repetitive Transcranial Magnetic Stimulation(rTMS) Treatment Based on Personalized Modulation of Electroencephalography Promotes Symptom Remission in Major Depressive Disorder (MDD) - A Randomized Controlled Clinical Trial
• Estimated Study Start Date: May 2024
• Estimated Primary Completion Date: May 2026
• Estimated Study Completion Date: May 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: The Precision Group; Patients in the precision group will be treated with Individualized alpha frequency Transcranial Magnetic Stimulation (αTMS) Treatment.	Device: Individualized alpha frequency Transcranial Magnetic Stimulation (αTMS) Treatment; The target site for alpha frequency Transcranial Magnetic Stimulation (αTMS) was identified based on alterations in alpha band spectral connectivity, which were measured using four frontal electroencephalography (EEG) channels (F1, F3, F5, FC3) subsequent to 10Hz transcranial magnetic stimulation (TMS). Alpha band spectral connectivity refers to the degree of similarity between the spectral waveforms of the alpha band across channels. The alpha frequency stimulation rate was defined as the highest spectral peak within the alpha band ranging from 7 to 13 Hz of the target channel. Each treatment cycle consisted of 20 daily sessions over a 4-week span, and stimulation was administered for 2 seconds every minute for a total duration of 20 minutes at 80% of the individual's motor threshold.
Active Comparator: The Conventional Group; Patients in the conventional group will be treated with 10Hz-frequency TMS over the left dorsolateral prefrontal cortex (DLPFC).	Device: 10Hz-frequency TMS treatment over the left dorsolateral prefrontal cortex (DLPFC); Prefrontal Transcranial Magnetic Stimulation (TMS) therapy repeated daily over 4 weeks (20 sessions) is US Food and Drug Administration (FDA) approved for treating Major Depressive Disorder in adults who have not responded to prior antidepressant medications. The strongest evidence supports high-frequency treatment over the left dorsolateral prefrontal cortex (DLPFC). The common stimulation frequency is 10Hz. It is usually applied for a duration of 4 weeks, 5 days a week.

Outcome Measures

Primary Outcome Measures :

1. the response rate [ Time Frame: 4 weeks ]
   It will be determined by Hamilton Depression Scale(HAMD-24 item) score. Specifically, the response rate is defined as a 30% decrease in HAMD score from those measured at baseline.

Secondary Outcome Measures :

1. complete remission rate [ Time Frame: 4 weeks ]
   It will be determined by Hamilton Depression Scale(HAMD-24 item) score. Specifically, the complete remission rate is defined as the HAMD score of less than 8 at the follow-up point.
2. alpha band spectral connectivity in electroencephalogram (EEG) parameters [ Time Frame: 4 weeks ]
   It will be determined by the changes of alpha band spectral connectivity in EEG parameters. Specifically, the EEG index is the change in alpha band spectral connectivity before and after a single TMS intervention, representing the functional connectivity between the frontal lobe and other brain regions across the entire brain.
3. Evaluation of therapeutic effect [ Time Frame: 4 weeks ]
   It will be determined using the criteria for the global improvement(GI) from Clinical Global Impression(CGI). Specifically, the global improvement(GI) will be rated by the clinician for the degree of improvement in the subject's current condition compared to baseline at enrollment on an 8-point scale from 0-7(the rating "1" refers to significant progress, and the rating "2" refers to progress, etc.).

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• The diagnosis of participants should be made in accordance to the diagnostic criteria described for Major Depressive Disorder (MDD) of the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-V).
• be willing to receive neuromodulation therapy and sign the written informed consent
• an age of 18-65 years
• The patient's medication regimen is based on only one antidepressant, and the medication regimen is not adjusted as much as possible during the treatment period.
• Having a total score of not less than 20 on the Hamilton Depression Rating Scale (HAMD-24).
• sufficient hearing or reading ability

Exclusion Criteria:

• History of electroconvulsive therapy (ECT)
• Presence of metallic foreign bodies near the stimulation coil or stimulation scalp, e.g., intracranial metal implants, cochlear implants, built-in pulse generators (brain pacemakers, cardiac pacemakers)
• Epilepsy
• Pregnancy
• History of head injury
• Mental disorders such as schizophrenia, bipolar disorder, schizoid personality disorder, alcohol/drug abuse or dependence, etc.
• Serious physical illnesses
• Taking medication that lowers the seizure threshold
• Participating in any clinical trial within 30 days before the baseline
• Other situations judged by the investigators not to be suitable for the clinical trial

Contacts and Locations

Contacts

Contact: TianHong Zhang, Doctor; 13127577024; zhang_tianhong@126.com

Locations

China, Shanghai

Shanghai Mental Health Center

Shanghai, Shanghai, China, 200030

Contact: TianHong Zhang, Doctor 13127577024 zhang_tianhong@126.com

Sponsors and Collaborators

Shanghai Mental Health Center

National Natural Science Foundation of China

Shanghai Municipal Science and Technology Commission

Shanghai Jiao Tong University School of Medicine

Investigators

• Principal Investigator: TianHong Zhang, Doctor; Shanghai Mental Health Center

More Information

• Responsible Party: Tianhong ZHANG, Associate Professor, Shanghai Mental Health Center
• ClinicalTrials.gov Identifier: NCT06385405
• Other Study ID Numbers: 2024y0423
• First Posted: April 26, 2024
• Last Update Posted: May 9, 2024
• Last Verified: May 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tianhong ZHANG, Shanghai Mental Health Center:

Transcranial magnetic stimulation(TMS); electroencephalogram (EEG); Personalized treatment; machine learning

Additional relevant MeSH terms:

Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Behavioral Symptoms