Clinical trial NCT06784388: Personalized DBS Targeting for Treating Depression
Official title: Clinical Application of Personalized DBS Target Optimization for Treating Depression
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Treatment-resistant Depression (TRD)
Keywords: Treatment-resistant depression (TRD)
DBS
stimulation target
stimulation parameters
neural biomarker
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2025-01-20
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Hamilton Rating Scale for Depression (HAMD) score during the DBS treatment phase relative to preoperative baseline
timeFrame: at baseline and after 442 day
measure: Changes in HAMD scores during the efficacy observation phase after DBS shutdown
timeFrame: Two months after 442 days
Secondary outcomes:
measure: the score of Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Every 2 weeks between day 21 and day 442
measure: the score of multi-lingual Hypomania Check List(C-SSRS)
timeFrame: Every 2 weeks between day 21 and day 442
measure: the score of Hamilton Anxiety Scale(HAMA)
timeFrame: Every 2 weeks between day 21 and day 442
measure: the score of the Oxford Depression Questionnaire(ODQ)
timeFrame: Every 2 weeks between day 21 and day 442
measure: the score of THINC-integrated tool(THINC-it)
timeFrame: Every 2 weeks between day 21 and day 442
measure: the score of Visual Analogue Scale-Depression(VAS-D)
timeFrame: Every 2 weeks between day 21 and day 442
measure: the score of HAMD-6 item(HAMD-6)
timeFrame: Every 2 weeks between day 21 and day 442
measure: the score of Patient Health Questionnaire-9( PHQ-9)
timeFrame: Every 2 weeks between day 21 and day 442
measure: the score of Beck Depression Inventory(BDI)
timeFrame: Every 2 weeks between day 21 and day 442
measure: the score of Visual Analogue Scale-Anxiety(VAS-A)
timeFrame: Every 2 weeks between day 21 and day 442
measure: the score of General Anxiety Disorder-7(GAD-7)
timeFrame: Every 2 weeks between day 21 and day 442
measure: the score of Beck Anxiety Inventory(BAI)
timeFrame: Every 2 weeks between day 21 and day 442
measure: the score of Immediate Mood Scale(IMS)
timeFrame: Every 2 weeks between day 21 and day 442
measure: the score of Quick Inventory of Depressive Symptomatology, Self-Rated(QIDS-SR)
timeFrame: Every 2 weeks between day 21 and day 442
measure: Adverse events
timeFrame: Perioperative and every 2 weeks between day 21 and day 442
Other outcomes:
Locations:
city: Hangzhou City
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References:
citation: 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.
citation: 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.