Early Identification of TRD and Construction and Clinical Validation of NTBS Precision Technology

Zhejiang University

Status: Enrolling

Conditions: Treatment-Resistant Depression

Treatments: Device: Sham stimulation; Device: non-invasive transcranial deep brain stimulation with closed-loop; Device: non-invasive transcranial deep brain stimulation; Device: Motor cortex stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT05777876

2023C03077

Details and patient eligibility

About

The goal of this clinical trial is to learn about the characteristics, identify early and intervene effectively in time in Treatment-Resistant Depression. The main questions are: • TRD is difficult to identify early and lacks objective detection indicators; • Existing treatment strategies for TRD are associated with side effects and high treatment resistance; • Current non-invasive brain stimulation therapy lacks precision.

it aims to answer are: • Construct a multimodal TRD early identification model based on clinical characteristics, blood factors, functional magnetic resonance and brain electrophysiological indicators; • Develop non-invasive transcranial deep brain stimulation technology based on focused electric field; • In TRD patients, an individualized non-invasive transcranial deep electrical stimulation technology based on precise magnetic resonance targets and EEG phase guidance was constructed.

Participants will:• be collected data multiple times including clinical symptoms, peripheral biology, functional magnetic resonance, electrophysiology and other clinical data before and after the intervention; • receive non-invasive transcranial deep brain stimulation or sham stimulation of different deep brain target points; • be collected EEG data while receiving stimulation.

Researchers will • compare the biological characteristics of TRD, n-TRD patients and health controls to build early identification models and find potential spatial and temporal intervention targets dependent on TRD status; • verify the safety of non-invasive transcranial deep brain stimulation device in health controls; • compare TRD with different modes of stimulation to find the best treatment plan for non-invasive transcranial deep brain stimulation and verify safety.

Full description

At present, those who are still ineffective after two or more full-dose antidepressants are called treatment-resistant depression (Treatment-Resistant Depression, TRD). Patients with TRD have increased suicide risk, increased medical expenditure, decreased quality of life, and increased disease burden. Existing diagnosis is verified by clinical symptoms, continuous attempts of antidepressant treatment programs, and observation of efficacy, lack of early identification of biological markers, and the main treatment strategies for TRD patients are related to side effects and high treatment resistance. Therefore, how to identify TRD early and intervene in time is an important direction of current depression research.

Based on the previous research work, this project plans to establish a prospective cohort study of clinical cases, and to discover the clinical characteristics of TRD, factors carried by peripheral blood and exosomes (Hypocretin, Brain-derived neurotrophic fact, Reelin, N-methyl-D- Aspartic acid receptor), functional magnetic resonance and brain electrophysiological indicators and other objective biological markers, using multi-modal fusion to establish an early identification model for TRD. At the same time, we plan to analyze the abnormal brain network characteristics and abnormal EEG phase characteristics of TRD, in order to search for abnormalities through multi-dimensional data Potential spatial and temporal intervention targets dependent on TRD status.

Recently, a new non-invasive transcranial electrical stimulation method, namely Temporal Interference Stimulation (TIS), can non-invasively stimulate area-specific Focus on the deep brain area without affecting the upper brain area of the target area. This project will carry out the research and development of the principle prototype of the non-invasive transcranial deep electric Clinical curative effect comparison and safety evaluation, so as to verify the best TIS intervention target, on this basis, according to the above-explored TRD state-dependent EEG signals, through spontaneous synchronous oscillation signals between different channels on the neural loop , to achieve individualized neuromodulation. Finally, a diagnosis and treatment model for early identification of refractory depression and non-invasive transcranial deep electrical stimulation technology will be established to provide new guidance for TRD treatment.

Enrollment: 400 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• This episode meets the diagnostic criteria of DSM-5 major depression, and is not accompanied by psychotic symptoms in the first episode or relapse of unmedicated depression;
• 24 item Hamilton Depression Scale (HAMD-24)≥20;
• Age 18-60, gender unlimited;
• right hand;
• Han Chinese;
• Sign a written informed consent and be willing to participate in the study and be evaluated.

Exclusion criteria

• Comorbidities with other mental disorders, including schizophrenia, mental retardation, substance dependence, etc.
• Patients with metal objects in the body or other contraindications for MRI scanning;
• Suffering from a serious or unstable physical disease;
• Positive urine HCG test results of pregnant and lactating women and women of childbearing age during screening;
• Other conditions deemed unsuitable for participation in the clinical trial by the investigator.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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400 participants in 9 patient groups

non-TRD

No Intervention group

Description:

Patients with first episode or relapse of untreated depression group are treated with escitalopram for 8 weeks, and if effective, they are included in the n-TRD group. If ineffective, Venlafaxine is used for full treatment for 8 weeks; if effective, the patients are included in the non-TRD group. The subjects get clinical evaluation, blood sample collection, magnetic resonance scanning, and electrophysiological monitoring.

TRD Target stimulation A

Experimental group

Description:

Patients do not respond favorably to two antidepressants. The subjects get clinical evaluation, blood sample collection, magnetic resonance scanning, and electrophysiological monitoring. Regimen: Receiving TIS intervention with target A (Characteristic abnormal brain region targets based on data-driven exploration) for 10 times, once a day (except weekends and holidays) for 2 weeks. Stimulation（130Hz, 2mA total current intensity, each stimulation lasts for 30 minutes, 15 seconds respectively for import and exit).

Treatment:

Device: non-invasive transcranial deep brain stimulation

TRD Target stimulation B

Experimental group

Description:

Patients do not respond favorably to two antidepressants. The subjects get clinical evaluation, blood sample collection, magnetic resonance scanning, and electrophysiological monitoring. Regimen: Receiving TIS intervention with target B (Characteristic abnormal brain region targets based on data-driven exploration) for 10 times, once a day (except weekends and holidays) for 2 weeks. Stimulation（130Hz, 2mA total current intensity, each stimulation lasts for 30 minutes, 15 seconds respectively for import and exit).

Treatment:

Device: non-invasive transcranial deep brain stimulation

TRD Target stimulation C

Experimental group

Description:

Patients do not respond favorably to two antidepressants. The subjects get clinical evaluation, blood sample collection, magnetic resonance scanning, and electrophysiological monitoring. Regimen: Receiving TIS intervention with target C (Characteristic abnormal brain region targets based on data-driven exploration) for 10 times, once a day (except weekends and holidays) for 2 weeks. Stimulation（130Hz, 2mA total current intensity, each stimulation lasts for 30 minutes, 15 seconds respectively for import and exit).

Treatment:

Device: non-invasive transcranial deep brain stimulation

TRD sham stimulation

Sham Comparator group

Description:

Patients do not respond favorably to two antidepressants. The subjects get clinical evaluation, blood sample collection, magnetic resonance scanning, and electrophysiological monitoring. Regimen: sham stimulation for 10 times, once a day (except weekends and holidays) for 2 weeks. Stimulation（130Hz, 2mA total current intensity, each stimulation lasts for 30 seconds, total wearing the instrument for 30 minutes)

Treatment:

Device: Sham stimulation

TRD closed-loop stimulation

Experimental group

Description:

Patients do not respond favorably to two antidepressants. The subjects get clinical evaluation, blood sample collection, magnetic resonance scanning, and electrophysiological monitoring. Patients receive closed-loop stimulation guided by EEG phase, and the stimulation target is the effective deep brain region target verified in this study. Regimen: stimulation for 10 times, once a day (except weekends and holidays) for 2 weeks. Stimulation（130Hz, 2mA total current intensity, each stimulation lasts for 30 minutes, 15 seconds respectively for import and exit)

Treatment:

Device: non-invasive transcranial deep brain stimulation with closed-loop

HC experimental stimulation

Experimental group

Description:

The subjects get clinical evaluation, blood sample collection, magnetic resonance scanning, and electrophysiological monitoring. HC will receive TIS intervention in the exercise area for one time, the stimulation scheme adopted 20 Hz and 2mA total current intensity, and each stimulation lasted for 30 minutes (15 seconds respectively for lead-in and withdrawal)

Treatment:

Device: Motor cortex stimulation

HC sham stimulation

Sham Comparator group

Description:

The subjects get clinical evaluation, blood sample collection, magnetic resonance scanning, and electrophysiological monitoring. Electrode placement, current intensity and intervention times are consistent with those of TIS regimen. 20 Hz, 2mA total current intensityis used, but only lasted for 30 seconds, and then the current is 0 for a total of 30 minutes.

Treatment:

Device: Sham stimulation

HC observation

No Intervention group

Description:

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