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

NCT05777876 | Unknown

• 1 other identifier: 2023C03077
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Treatment-Resistant Depression

Keywords

non-invasive transcranial deep brain stimulation; Temporal Interference Stimulation; depression; early recognition

Outcome Measures

Primary Outcomes (1)

• 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. Remission is defined as HAM-D24 ≤8. A reduction of 50% or more in total score from Baseline indicates clinical response.

  Baseline to end of stimulation period, an average of 14 days

Secondary Outcomes (8)

• Change of Hamilton Depression Scale (24-items) score

  7 days and 28 days

• Change in the rate of Beck Scale of Suicidal Ideation score

  Baseline to end of stimulation period, an average of 14 days.

• Change in the rate of Hamilton Anxiety Scale score

  Baseline to end of stimulation period, an average of 14 days

• Change in the score of THINC-it.

  Baseline to end of stimulation period, an average of 14 days

• Treatment Emergent Symptom Scale

  through study completion, an average of 14 days.

Study Arms (9)

non-TRD

NO INTERVENTION

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

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).

Device: non-invasive transcranial deep brain stimulation

TRD Target stimulation B

EXPERIMENTAL

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).

Device: non-invasive transcranial deep brain stimulation

TRD Target stimulation C

EXPERIMENTAL

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).

Device: non-invasive transcranial deep brain stimulation

TRD sham stimulation

SHAM COMPARATOR

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)

Device: Sham stimulation

TRD closed-loop stimulation

EXPERIMENTAL

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)

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

HC experimental stimulation

EXPERIMENTAL

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)

Device: Motor cortex stimulation

HC sham stimulation

SHAM COMPARATOR

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.

Device: Sham stimulation

HC observation

NO INTERVENTION

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

Interventions

non-invasive transcranial deep brain stimulation DEVICE

A new non-invasive transcranial deep brain stimulation, Temporal Interference Stimulation (TIS), can focus the stimulation region specifically on the deep brain region without affecting the upper level of the target region. At present, the safety of this method has been preliminarily verified in animals and healthy people, but the brain target of TRD treatment is not clear.

TRD Target stimulation A; TRD Target stimulation B; TRD Target stimulation C

Sham stimulation DEVICE

Electrodes will be placed in the same location on the head as that for the TI intervention; 30 seconds of electrical current will be delivered to the brain (compared to 30 minutes in the experimental intervention arm), therefore it is expected to elicit no changes in neural activity.

HC sham stimulation; TRD sham stimulation

Motor cortex stimulation DEVICE

Receive stimulation in the motor cortex stimulation instead of deep brain.

HC experimental stimulation

non-invasive transcranial deep brain stimulation with closed-loop DEVICE

Non-invasive transcranial deep brain stimulation devices based on closed-loop regulation of EEG can improve the accuracy of treatment.

TRD closed-loop stimulation

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead
• Zhejiang University: collaborator
• Kangci Hospital of Jiaxing: collaborator
• Wenzhou Seventh People's Hospital: collaborator
• Lishui Second People's Hospital: collaborator
• Huzhou Third People's Hospital: collaborator
• Binjiang Institute of Zhejiang University: collaborator
• Zhejiang Newways Medical Technology Co., Ltd: collaborator
• Hangzhou Lingnao Technology Co., Ltd: collaborator

Study Sites (1)

The First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Manli Huang, Professor

  Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manli Huang, Professor

CONTACT

13957162975; huangmanli@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2023
• First Posted: March 21, 2023
• Study Start: January 1, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: March 21, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)