Deep Brain Stimulation of the Nucleus Accumbens and Anterior Limb of the Internal Capsule in the Treatment of Refractory Schizophrenia

NCT07369401 | Not Yet Recruiting DMC

• 1 other identifier: MRCTA,ECFAH of FMU [2025]637
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

Schizophrenia is a lifelong psychiatric disorder with a prevalence rate of 0.559% and a lifetime prevalence rate of 0.588% among Chinese adults. It often causes social dysfunction and psychiatric disability, shortening patients' life expectancy by 10-25 years compared to the general population. Approximately 30% of patients are resistant to antipsychotic medications, and 60% of these do not respond to clozapine (ultra-refractory). DBS has shown definite efficacy in movement disorders and refractory obsessive-compulsive disorder (OCD) as well as major depressive disorder (MDD). Preliminary studies have indicated that DBS targeting sites such as the NAcc can improve symptoms in some schizophrenia patients. Additionally, abnormal white matter in the anterior limb of the internal capsule has been identified in refractory patients, providing a basis for exploring combined target stimulation. This study aims to investigate the efficacy and safety of deep brain stimulation of the Nucleus Accumbens and Anterior Limb of the Internal Capsule in the treatment of refractory schizophrenia. A randomized controlled (self-controlled) design is adopted. The statistical analysis unit generates a random allocation table using SAS software, and groups are assigned via central randomization. Both groups undergo three stimulation phases: DBS activation 2 weeks after surgery, 6 weeks of single-target stimulation followed by 2 weeks of shutdown, another 6 weeks of alternate single-target stimulation followed by 2 weeks of shutdown, and finally 6 weeks of combined dual-target stimulation. Trial Group 1 is stimulated sequentially at NAcc, Anterior Limb of the Internal Capsule, and dual targets; Trial Group 2 follows the reverse order for single-target stimulation before combined stimulation. Surgery is performed under general anesthesia by neurosurgeons with associate senior titles or above and extensive experience. After head frame placement, CT and MRI images are fused for targeting. Electrodes are implanted into the NAcc via the Anterior Limb of the Internal Capsule, and a pulse generator is placed under the clavicle and connected to the electrodes. Postoperative CT confirms electrode position. Trial devices are provided by Jingyu Medical Technology (Suzhou) Co., Ltd., including implantable neurostimulation systems, electrode leads, extension leads, and programming equipment. On-site follow-up is conducted at key time points: screening, baseline, 2 weeks postoperatively (DBS activation), 6 weeks after stimulation, 16 weeks postoperatively, and 24 weeks postoperatively, including scale assessments, physical examinations, and laboratory/imaging tests. The primary outcome measure was the reduction rate of the total PANSS score at 24 weeks after DBS implantation compared to baseline, with a 20% reduction defined as effective, assessed by independent psychiatric evaluators.

Conditions

Refractory Schizophrenia

Keywords

Deep Brain Stimulation; Refractory Schizophrenia; Nucleus Accumbens; Anterior Limb

Outcome Measures

Primary Outcomes (1)

• The reduction rate of the total PANSS score at 24 weeks

  The reduction rate of the total PANSS score at 24 weeks after DBS implantation compared to baseline. The reduction rate is (PANSS score at baseline - PANSS score at 24-weeks) / PANSS score at baseline. PANSS score was assessed by independent psychiatric evaluators.

  24 weeks after treatment

Secondary Outcomes (2)

• The proportion of effective treatment

  24 weeks after treatment

• The change value of the Clinical Global Impression (CGI) scale score at 24 weeks

  24 weeks after treatment

Study Arms (2)

Trial Group 1

EXPERIMENTAL

DBS is activated 2 weeks after implantation for NAcc-only stimulation. Stimulation is maintained for 6 weeks (until week 8 postoperatively), then shut down. Stimulation is reactivated at week 10 for anterior limb of the internal capsule-only stimulation, maintained for 6 weeks (until week 16 postoperatively), then shut down. Combined stimulation of the NAcc and anterior limb of the internal capsule is initiated at week 18 postoperatively, maintained for 6 weeks, followed by efficacy assessment.

Device: Deep Brain Stimulation

Trial Group 2

EXPERIMENTAL

DBS is activated 2 weeks after implantation for anterior limb of the internal capsule-only stimulation. Stimulation is maintained for 6 weeks (until week 8 postoperatively), then shut down. Stimulation is reactivated at week 10 for NAcc-only stimulation, maintained for 6 weeks (until week 16 postoperatively), then shut down. Combined stimulation of the NAcc and anterior limb of the internal capsule is initiated at week 18 postoperatively, maintained for 6 weeks, followed by efficacy assessment.

Device: Deep Brain Stimulation

Interventions

Deep Brain Stimulation DEVICE

An assessment is conducted 7 days postoperatively. DBS is activated 2 weeks after implantation for NAcc-only stimulation. Stimulation is maintained for 6 weeks (until week 8 postoperatively), then shut down. Stimulation is reactivated at week 10 for anterior limb of the internal capsule-only stimulation, maintained for 6 weeks (until week 16 postoperatively), then shut down. Based on the participant's vital signs and motor responses to stimulation, initial parameters are set as: 2.5-7.5 V, pulse width 60-210 µs, frequency 80-210 Hz. During the stabilization phase, an independent clinical programmer adjusts parameters individually for each patient based on clinical status and provides guidance according to symptom changes. Patients are not informed of any adjustments. To maximize therapeutic efficacy, the adjustment sequence is: (1) increase voltage up to 7.5 V; (2) increase pulse width or frequency up to 210 µs/Hz; (3) change contacts or modes (monopolar negative or bipolar negative).

Trial Group 1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18-55 years (inclusive) at the time of signing the informed consent form, male or non-pregnant female;
• Meets the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for schizophrenia;
• Schizophrenia disease course ≥ 5 years before screening;
• Meets the 2016 TRRIP criteria for refractory/ultra-refractory schizophrenia: previous treatment with ≥ 2 non-clozapine antipsychotics at adequate dose (≥ 600mg/day chlorpromazine equivalent) and duration (≥ 12 weeks) with no response or intolerance, or clozapine at adequate dose (≥ 300mg/day or plasma concentration ≥ 350ng/ml) and duration (≥ 12 weeks) with no response or intolerance, plus moderate or greater symptom severity;
• PANSS total score ≥ 70 at screening and baseline;
• No changes in medication regimen in the past 2 months;
• The patient and their guardian have been fully informed and signed the informed consent form.

You may not qualify if:

• Comorbid with epilepsy, severe cognitive impairment (Mini-Mental State Examination \[MMSE\] score \< 10), organic mental disorder, paranoid personality disorder, mental retardation, or addiction (other than nicotine);
• Has implanted devices such as cochlear implants or cardiac pacemakers, or has undergone surgery that may affect the trial within 6 months;
• Has contraindications to DBS implantation and is deemed unsuitable for surgery by the investigator;
• Has participated in other drug/medical device clinical trials within 3 months before screening;
• Confirmed HIV-positive;
• Pregnant/lactating women, women of childbearing age with positive HCG/urine pregnancy test at screening, those unable to use effective contraception during the trial, or those planning to conceive within 3 months after trial initiation;
• Other conditions deemed unsuitable for participation by the investigator.

Sponsors & Collaborators

• First Affiliated Hospital of Fujian Medical University: lead

MeSH Terms

Conditions

Schizophrenia, Treatment-Resistant

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Central Study Contacts

Kang Dezhi, Professor

CONTACT

0591-87982798; kdz99988@vip.sina.com

Yao Peisen, professor of medicine

CONTACT

86+18650084102

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and assessing physicians are blinded, while programming physicians are unblinded. Initial stimulation parameters are 2.5-7.5 V, 60-210 μs, and 80-210 Hz. During the stabilization phase, parameters are adjusted individually in the order of "voltage → pulse width/frequency → contacts/mode", and patients are not informed of adjustments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: January 18, 2026
• First Posted: January 27, 2026
• Study Start: January 20, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share