Personalized DBS Targeting for Treating Depression

NCT ID: NCT06784388

Last Updated: 2025-01-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-05
• Study Completion Date: 2028-12-30

Brief Summary

The goal of this clinical trial is to optimize the target brain areas for deep brain stimulation (DBS) for depression based on personalized brain imaging and stereo-electroencephalography（SEEG), to administer long-term DBS treatment in the target brain areas, to assess the effectiveness and safety of DBS for refractory depression and to validate the method of personalized optimization of DBS targets. The main questions it aims to answer are:

1. Where is the optimal DBS target brain region for each patient?

2. What are the optimal DBS parameters for each patient ?

3. What are the neural biomarkers of depression symptoms for each patient?

4. Are the optimized DBS strategies effective in treating refractory depression?

Detailed Description

This clinical study is a prospective clinical trial focused on the personalized optimization methods and applications of DBS targets for depression.

The study is divided into 4 phases and in each phase and participants will complete different tasks:

1. The preoperative assessment phase:Lasting 7 days, participants will be required to complete preoperative symptom assessments, brain imaging, and task-state functional magnetic resonance imaging(fMRI) assessment.

2. The SEEG assessment phase: Lasting 14 days, participants will be implanted SEEG electrodes and complete a series of SEEG assessments.

3. The DBS treatment phase: Lasting 421 days, participants will be implanted a DBS device and treated with the DBS. During this period, participants will be required to complete the appropriate depressive symptom assessment tasks, as well as follow-up visits every 2 weeks.

4. The efficacy observation phase after DBS shutdown: Lasting 2 months, if the participant has a good outcome at the DBS for depression phase, the electrical stimulation will be shut down for 2 months to observe the maintenance of the efficacy of the treatment, during which time, if the symptoms rebound, the DBS treatment will be restarted until the completion of the study at the end of the 2-month period. During this time participants will be required to complete the appropriate depressive symptom assessment tasks, and follow-up visits every 2 weeks.

Conditions

Treatment-resistant Depression (TRD)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Depression

Group Type: EXPERIMENTAL

Deep Brain Stimulation(DBS)

Intervention Type: DEVICE

During the DBS treatment phase, the DBS device will apply electrical stimulation to the patient's target brain regions using a specific strategy, and if the efficacy of this phase is not satisfactory, electrical stimulation will continue to be applied during the efficacy observation phase after DBS shutdown.

Esketamine

Intervention Type: DRUG

SEEG intraoperative experiment: patients will be implanted with microelectrodes and connected to an electrophysiological recorder under local anesthesia. Intraoperative neurophysiological baseline will be recorded for 5 minutes, and esketamine will be injected intravenously at a dose of 0.5 mg/kg, and neurophysiological recordings will be continued for 15 minutes to observe the neuronal electrophysiological changes in various brain regions and target points.

Interventions

Deep Brain Stimulation(DBS)

During the DBS treatment phase, the DBS device will apply electrical stimulation to the patient's target brain regions using a specific strategy, and if the efficacy of this phase is not satisfactory, electrical stimulation will continue to be applied during the efficacy observation phase after DBS shutdown.

Intervention Type: DEVICE

Esketamine

SEEG intraoperative experiment: patients will be implanted with microelectrodes and connected to an electrophysiological recorder under local anesthesia. Intraoperative neurophysiological baseline will be recorded for 5 minutes, and esketamine will be injected intravenously at a dose of 0.5 mg/kg, and neurophysiological recordings will be continued for 15 minutes to observe the neuronal electrophysiological changes in various brain regions and target points.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. A psychiatrist-confirmed diagnosis of major depressive disorder in accordance with the Diagnostic And Statistical Manual Of Mental Disorders.5th Ed (DSM-V);

2. A psychiatric examination by two trained psychiatrists and a diagnosis consistent with the DSM-V;

3. A history of depression of at least 12 months duration in depressed patients (including MECT) who have failed to respond to a full dose and course of treatment with 2 or more antidepressants of different mechanisms;

4. A 17-item score on the HAMD scale ⩾ 20 at initial screening;

5. A score of ≤ 50 on the Gross Assessment of Functioning (GAF) scale;

6. The patient himself/herself or legal guardian was able to fully understand the therapy and agreed to enroll after signing an informed consent form.

Exclusion Criteria

1. Persons with severe or unstable cardiac, hepatic, renal, endocrine, hematologic, and other medical disorders and co-morbidities with psychotic symptoms, including personality disorders diagnosed by history, questioning, and clinical examination;

2. Persons with psychiatric disorders other than depression (except generalized anxiety);

3. Persons with a history of substance abuse within 12 months; persons with a previous history of epilepsy, and persons with febrile convulsions in childhood;

4. Patients with a history of suicide attempts within the past 6 months or more than 2 suicide attempts within the past 2 years;

5. Women who are breastfeeding, pregnant, and patients who are pregnant or intend to become pregnant during the clinical study;

6. Contraindications to DBS surgery and MRI;

7. Years of education less than or equal to 9 years;

8. Patients who are involuntarily hospitalized.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Junming Zhu, Ph.D.

Role: CONTACT

dr.zhujunming@zju.edu.cn

+86 13968055768

Facility Contacts

Yuxiao Yang, Ph.D.

Role: primary

yuxiao.yang@zju.edu.cn

+86 15088771810

References

Scangos KW, Khambhati AN, Daly PM, Makhoul GS, Sugrue LP, Zamanian H, Liu TX, Rao VR, Sellers KK, Dawes HE, Starr PA, Krystal AD, Chang EF. Closed-loop neuromodulation in an individual with treatment-resistant depression. Nat Med. 2021 Oct;27(10):1696-1700. doi: 10.1038/s41591-021-01480-w. Epub 2021 Oct 4.

Reference Type: BACKGROUND

PMID: 34608328 (View on PubMed)

Alagapan S, Choi KS, Heisig S, Riva-Posse P, Crowell A, Tiruvadi V, Obatusin M, Veerakumar A, Waters AC, Gross RE, Quinn S, Denison L, O'Shaughnessy M, Connor M, Canal G, Cha J, Hershenberg R, Nauvel T, Isbaine F, Afzal MF, Figee M, Kopell BH, Butera R, Mayberg HS, Rozell CJ. Cingulate dynamics track depression recovery with deep brain stimulation. Nature. 2023 Oct;622(7981):130-138. doi: 10.1038/s41586-023-06541-3. Epub 2023 Sep 20.

Reference Type: BACKGROUND

PMID: 37730990 (View on PubMed)

Other Identifiers

IR2024292

Identifier Type: -

Identifier Source: org_study_id