Clinical trial NCT05777876: Early Identification of TRD and Construction and Clinical Validation of NTBS Precision Technology
Official title: Early Identification of Treatment-resistant Depression and Construction and Clinical Validation of Non-invasive Transcranial Deep Brain Stimulation Precision Technology
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Treatment-Resistant Depression
Keywords: non-invasive transcranial deep brain stimulation
Temporal Interference Stimulation
depression
early recognition
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
Collaborators: name: Zhejiang University
name: Kangci Hospital of Jiaxing
name: Wenzhou Seventh People's Hospital
name: Lishui Second People's Hospital
name: Huzhou Third People's Hospital
name: Binjiang Institute of Zhejiang University
name: Zhejiang Newways Medical Technology Co., Ltd
name: Hangzhou Lingnao Technology Co., Ltd
First posted: 2023-03-21
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hamilton Depression Scale (24-items) Total Score Change
timeFrame: Baseline to end of stimulation period, an average of 14 days
Secondary outcomes:
measure: Change of Hamilton Depression Scale (24-items) score
timeFrame: 7 days and 28 days
measure: Change in the rate of Beck Scale of Suicidal Ideation score
timeFrame: Baseline to end of stimulation period, an average of 14 days.
measure: Change in the rate of Hamilton Anxiety Scale score
timeFrame: Baseline to end of stimulation period, an average of 14 days
measure: Change in the score of THINC-it.
timeFrame: Baseline to end of stimulation period, an average of 14 days
measure: Treatment Emergent Symptom Scale
timeFrame: through study completion, an average of 14 days.
measure: Change in neuroimaging using functional magnetic resonance
timeFrame: Baseline, 14 days
measure: Change in electroencephalogram
timeFrame: through study completion, an average of 14 days.
measure: Change of blood factor levels
timeFrame: Baseline, 14 days
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: Manli Huang, Professor
role: PRINCIPAL_INVESTIGATOR
References: