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

Официальное название

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 Prospective, Single-Center, Double-Blind, Randomized Controlled Study

Обзор

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.

Вмешательства

• Устройство Deep Brain Stimulation
  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
• Устройство Deep Brain Stimulation
  An assessment is conducted 7 days postoperatively. 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.Based on the participant's vital signs and motor responses to stimulation, initial parameters are set as: 2.5-7.5 V, pulse

Первичные конечные точки

• The reduction rate of the total PANSS score at 24 weeks [Срок оценки: 24 weeks after treatment]

Вторичные конечные точки (2)

• The proportion of effective treatment [Срок оценки: 24 weeks after treatment]
• The change value of the Clinical Global Impression (CGI) scale score at 24 weeks [Срок оценки: 24 weeks after treatment]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07369401 · MRCTA,ECFAH of FMU [2025]637

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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