Personalized DBS Targeting for Treating Depression

NCT06784388 | Recruiting Early Phase 1 FDA Drug FDA Device

• 1 other identifier: IR2024292
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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. 1.Where is the optimal DBS target brain region for each patient?
2. 2.What are the optimal DBS parameters for each patient ?
3. 3.What are the neural biomarkers of depression symptoms for each patient?
4. 4.Are the optimized DBS strategies effective in treating refractory depression?

Conditions

Treatment-resistant Depression (TRD)

Keywords

Treatment-resistant depression (TRD); DBS; stimulation target; stimulation parameters; neural biomarker

Outcome Measures

Primary Outcomes (2)

• Change in Hamilton Rating Scale for Depression (HAMD) score during the DBS treatment phase relative to preoperative baseline

  Improvement is defined as a 25-49% reduction in Hamilton Rating Scale for Depression (HAMD) score relative to the preoperative baseline; response is defined as a ≥50% reduction in HAMD score relative to the preoperative baseline; and remission is defined as a HAMD score ≤8.

  at baseline and after 442 day

• Changes in HAMD scores during the efficacy observation phase after DBS shutdown

  Rebound is defined as a HAMD ≥18 in the subsequent follow-up period if the patient has an initial assessment of HAMD ≤8 in the efficacy observation phase after DBS shutdown, and rebound is defined as a HAMD score more than 2 times the initial assessment or 20 in the subsequent follow-up period if the patient has an initial assessment of HAMD \>8 in that phase.

  Two months after 442 days

Secondary Outcomes (15)

• the score of Montgomery-Asberg Depression Rating Scale (MADRS)

  Every 2 weeks between day 21 and day 442

• the score of multi-lingual Hypomania Check List(C-SSRS)

  Every 2 weeks between day 21 and day 442

• the score of Hamilton Anxiety Scale(HAMA)

  Every 2 weeks between day 21 and day 442

• the score of the Oxford Depression Questionnaire(ODQ)

  Every 2 weeks between day 21 and day 442

• the score of THINC-integrated tool(THINC-it)

  Every 2 weeks between day 21 and day 442

Study Arms (1)

Depression

EXPERIMENTAL

Device: Deep Brain Stimulation(DBS); Drug: Esketamine

Interventions

Esketamine 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.

Depression

Deep Brain Stimulation(DBS) 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.

Depression

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

Related Publications (2)

• 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 RESULT

• 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.

  PMID: 37730990 RESULT

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Deep Brain Stimulation; Esketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Central Study Contacts

Junming Zhu, Ph.D.

CONTACT

+86 13968055768; dr.zhujunming@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 14, 2025
• First Posted: January 20, 2025
• Study Start: January 5, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2028
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

CN (1)