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

Fujian Medical University (FJMU)

Status: Not yet enrolling

Conditions: Refractory Schizophrenia

Treatments: Device: Deep Brain Stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT07369401

MRCTA,ECFAH of FMU [2025]637

Details and patient eligibility

About

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.

Enrollment: 10 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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10 participants in 2 patient groups

Trial Group 1

Experimental group

Description:

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.

Treatment:

Device: Deep Brain Stimulation

Device: Deep Brain Stimulation

Trial Group 2

Experimental group

Description:

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.

Treatment:

Device: Deep Brain Stimulation

Device: Deep Brain Stimulation