Personalized DBS Targeting for Treating Depression

Official title

Clinical Application of Personalized DBS Target Optimization for Treating Depression

Overview

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.

Interventions

• Device 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.
• Drug 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.

Primary outcome measures

• Change in Hamilton Rating Scale for Depression (HAMD) score during the DBS treatment phase relative to preoperative baseline [Time frame: at baseline and after 442 day]
• Changes in HAMD scores during the efficacy observation phase after DBS shutdown [Time frame: Two months after 442 days]

Secondary outcome measures (12)

• the score of Montgomery-Asberg Depression Rating Scale (MADRS) [Time frame: Every 2 weeks between day 21 and day 442]
• the score of multi-lingual Hypomania Check List(C-SSRS) [Time frame: Every 2 weeks between day 21 and day 442]
• the score of Hamilton Anxiety Scale(HAMA) [Time frame: Every 2 weeks between day 21 and day 442]
• the score of the Oxford Depression Questionnaire(ODQ) [Time frame: Every 2 weeks between day 21 and day 442]
• the score of THINC-integrated tool(THINC-it) [Time frame: Every 2 weeks between day 21 and day 442]
• the score of Visual Analogue Scale-Depression(VAS-D) [Time frame: Every 2 weeks between day 21 and day 442]
• the score of HAMD-6 item(HAMD-6) [Time frame: Every 2 weeks between day 21 and day 442]
• the score of Patient Health Questionnaire-9( PHQ-9) [Time frame: Every 2 weeks between day 21 and day 442]
• the score of Beck Depression Inventory(BDI) [Time frame: Every 2 weeks between day 21 and day 442]
• the score of Visual Analogue Scale-Anxiety(VAS-A) [Time frame: Every 2 weeks between day 21 and day 442]
• the score of General Anxiety Disorder-7(GAD-7) [Time frame: Every 2 weeks between day 21 and day 442]
• the score of Beck Anxiety Inventory(BAI) [Time frame: Every 2 weeks between day 21 and day 442]

Eligibility criteria

Inclusion criteria

• A psychiatrist-confirmed diagnosis of major depressive disorder in accordance with the Diagnostic And Statistical Manual Of Mental Disorders.5th Ed (DSM-V);
• A psychiatric examination by two trained psychiatrists and a diagnosis consistent with the DSM-V;
• 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;
• A 17-item score on the HAMD scale ⩾ 20 at initial screening;
• A score of ≤ 50 on the Gross Assessment of Functioning (GAF) scale;
• 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

• 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;
• Persons with psychiatric disorders other than depression (except generalized anxiety);
• Persons with a history of substance abuse within 12 months; persons with a previous history of epilepsy, and persons with febrile convulsions in childhood;
• Patients with a history of suicide attempts within the past 6 months or more than 2 suicide attempts within the past 2 years;
• Women who are breastfeeding, pregnant, and patients who are pregnant or intend to become pregnant during the clinical study;
• Contraindications to DBS surgery and MRI;
• Years of education less than or equal to 9 years;
• Patients who are involuntarily hospitalized.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou

Publications

• 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. PMID 34608328
• 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/ PMID 37730990

Identifiers

NCT: NCT06784388 · IR2024292

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗