SEEG-Guided DBS for Schizophrenia
22 de junho de 2026 atualizado por: Bomin Sun, Ruijin Hospital
Deep Brain Stimulation for Treatment-Refractory Schizophrenia: Individualized Target Selection and Efficacy
This is a prospective, randomized, interventional study designed to evaluate the efficacy and safety of SEEG-guided deep brain stimulation (DBS) for symptom improvement in patients with treatment-resistant schizophrenia.
Using stereo-electroencephalography (SEEG) to record brain activity, we will identify specific abnormal electrophysiological targets and signal features associated with clinical symptoms, followed by a 12-month open-label stimulation period.
The study is conducted in three stages: Stage 1 consists of SEEG brain mapping, screening of intervention targets, and optimization of stimulation parameters; Stage 2 consists of DBS implantation surgery and further optimization of stimulation parameters; Stage 3 is a randomized crossover treatment phase, followed by an open-label treatment period.
Visão geral do estudo
Status
Recrutamento
Intervenção / Tratamento
Descrição detalhada
This clinical trial aims to systematically evaluate the efficacy and safety of SEEG-guided target screening combined with individualized deep brain stimulation (DBS) for treatment-refractory schizophrenia.
The study first employs Stereoelectroencephalography (SEEG) electrodes as the core tool to establish a personalized, minimally invasive neuromodulation surgical framework. After SEEG electrode implantation, researchers will collect and analyze high-spatiotemporal-resolution electrophysiological data during both resting-state and task-state conditions, as well as identify characteristic electrophysiological biomarkers that correlate with clinical symptoms.
Secondly, electrical stimulation is delivered through the SEEG contacts to functionally verify candidate targets in different brain regions. By stimulating specific targets and observing immediate symptomatic or physiological responses, we validate the effects on neural circuits and confirm their functional relevance prior to any permanent intervention. For targets that show preliminary efficacy, we further apply externalized chronic stimulation to continuously monitor symptom improvement and potential adverse effects.
After determine the optimal targets and the intervention is confirmed to be both effective and safe, we implant a permanent brain pacemaker (DBS device). During the efficacy follow-up phase, we employ a randomized crossover design, which is then followed by an open-label period. These two stages enable thorough assessment of clinical efficacy. Meanwhile, we also collect multidimensional data (clinical symptoms, cognition, and neuroimaging) to explore the circuit mechanisms of stimulation.
Tipo de estudo
Intervencional
Inscrição (Estimado)
46
Estágio
- Não aplicável
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Contato de estudo
- Nome: Shuo Ma, PhD
- Número de telefone: 86+15000838003
- E-mail: ms13144@rjh.com.cn
Locais de estudo
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Shanghai Municipality
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Shanghai, Shanghai Municipality, China, 200025
- Recrutamento
- Ruijin Hospital, Shanghai Jiaotong University School of Medicine
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Contato:
- Shuo Ma, PhD
- Número de telefone: 86+15000838003
- E-mail: ms13144@rjh.com.cn
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-
Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
Aceita Voluntários Saudáveis
Não
Descrição
Inclusion Criteria:
- Meets the International Classification of Diseases, 10th Revision (ICD-10) diagnostic criteria for schizophrenia.
- Male or female, aged 18 to 55 years, with stable vital signs.
- Currently presents with prominent psychotic symptoms, assessed as moderate or severe by the Positive and Negative Syndrome Scale (PANSS) or other equivalent scales.
- Exhibits impaired social functioning, assessed as moderate or severe impairment by the Social and Occupational Functioning Assessment Scale (SOFAS) or other equivalent scales.
- Has a history of sequential treatment with at least two antipsychotic medications of different chemical structures known for strong efficacy against positive symptoms. Treatment must have been at an adequate dose and for an adequate duration (continuous treatment at a therapeutic dose for more than 6 weeks per medication), with good treatment adherence.
- Has been on a stable antipsychotic medication regimen for at least one month prior to enrollment.
- Capable and willing to provide written informed consent.
- Demonstrates good compliance and is able to cooperate with all follow-up procedures.
Exclusion Criteria:
- Diagnosed with any psychiatric disorder other than schizophrenia.
- Presence of a severe personality disorder.
- History of severe neurological diseases, such as seizures or hemorrhagic stroke.
- Presence of structural brain abnormalities.
- Previous history of stereotactic neurosurgery.
- Contraindications to general anesthesia or stereotactic neurosurgery.
- Any current or anticipated condition-including medical, psychological, social, familial support, or geographical factors-that might compromise patient safety or interfere with successful participation in the study.
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Comparador Ativo: Stim ON-OFF
Participants randomized to the Stim ON-OFF arm will first undergo bilateral stereoelectroencephalography (SEEG) electrode implantation targeting brain regions associated with schizophrenia symptoms, followed by stimulation response assessments. Secondly, deep brain stimulation will be performed based on the electrophysiological recordings and stimulation assessment results. Thirdly, participants will receive active stimulation during the randomization phase for up to 12 weeks. The participants will then have their device turned off and receive sham stimulation during the crossover phase for up to 12 weeks. |
Phase 1 involves the stereotactic implantation of Stereoelectroencephalography (SEEG) electrodes.
Following implantation, comprehensive electrophysiological monitoring is conducted, including resting-state and task-state recordings, as well as acute electrical stimulation mapping.
This process aims to identify the specific pathological neural circuits and electrophysiological biomarkers associated with the patient's individual psychotic symptoms.
Phase 2 involves individualized deep brain stimulation (DBS).
Instead of relying solely on standardized anatomical landmarks, the DBS targets and parameters are precisely customized based on the individualized data acquired during the SEEG mapping phase.
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Comparador de Placebo: Stim OFF-ON
Participants randomized to the Stim OFF-ON arm will first undergo bilateral stereoelectroencephalography (SEEG) electrode implantation targeting brain regions associated with schizophrenia symptoms, followed by stimulation response assessments. Secondly, deep brain stimulation will be performed based on the electrophysiological recordings and stimulation assessment results. Thirdly, participants will have their device turned off and receive sham stimulation during the randomization phase for up to 12 weeks. The participants will then receive active stimulation during the crossover phase for up to 12 weeks. |
Phase 1 involves the stereotactic implantation of Stereoelectroencephalography (SEEG) electrodes.
Following implantation, comprehensive electrophysiological monitoring is conducted, including resting-state and task-state recordings, as well as acute electrical stimulation mapping.
This process aims to identify the specific pathological neural circuits and electrophysiological biomarkers associated with the patient's individual psychotic symptoms.
Phase 2 involves individualized deep brain stimulation (DBS).
Instead of relying solely on standardized anatomical landmarks, the DBS targets and parameters are precisely customized based on the individualized data acquired during the SEEG mapping phase.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Reduction Rate of PANSS Positive Subscale or SAPS
Prazo: Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
|
Positive symptoms are assessed using either the Positive and Negative Syndrome Scale (PANSS) positive subscale (P1-P7) or the Scale for the Assessment of Positive Symptoms (SAPS).
The PANSS evaluates positive, negative, and general psychopathology symptoms (total score range: 30-210).
The SAPS evaluates hallucinations, delusions, bizarre behavior, and positive formal thought disorder.
For both scales, higher scores indicate greater symptom severity.
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Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Reduction Rate of Auditory Hallucinations (Assessed by PSYRATS-AH)
Prazo: Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
|
The severity of auditory hallucinations is assessed using the Psychotic Symptom Rating Scales - Auditory Hallucinations subscale (PSYRATS-AH).
Higher scores indicate greater symptom severity.
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Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
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Reduction Rate of Delusions (Assessed by PSYRATS-D)
Prazo: Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
|
The severity of delusions is assessed using the Psychotic Symptom Rating Scales - Delusions subscale (PSYRATS-D).
Higher scores indicate greater symptom severity.
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Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
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Reduction Rate of Depressive Symptoms (Assessed by HAMD)
Prazo: Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
|
The severity of depression is assessed using the Hamilton Depression Rating Scale (HAMD).
Higher scores indicate greater severity of depressive symptoms.
The reduction rate will be calculated based on the change in the HAMD total score from baseline to each follow-up time point.
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Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
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Reduction Rate of Anxiety Symptoms (Assessed by HAMA)
Prazo: Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
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The severity of anxiety is assessed using the Hamilton Anxiety Rating Scale (HAMA).
Higher scores indicate greater severity of anxiety symptoms.
The reduction rate will be calculated based on the change in the HAMA total score from baseline to each follow-up time point.
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Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
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Improvement Rate of Cognitive Function (Assessed by MoCA)
Prazo: Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
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General cognitive performance is assessed using the Montreal Cognitive Assessment (MoCA).
The MoCA total score ranges from 0 to 30, with higher scores indicating better cognitive function.
Unlike symptom rating scales, the outcome here focuses on the positive percentage change (improvement rate) or absolute point increase in the MoCA total score from baseline to each follow-up time point.
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Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Publicações e links úteis
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Publicações Gerais
- Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH. Deep brain stimulation for treatment-resistant depression. Neuron. 2005 Mar 3;45(5):651-60. doi: 10.1016/j.neuron.2005.02.014.
- Limousin P, Krack P, Pollak P, Benazzouz A, Ardouin C, Hoffmann D, Benabid AL. Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med. 1998 Oct 15;339(16):1105-11. doi: 10.1056/NEJM199810153391603.
- Millier A, Schmidt U, Angermeyer MC, Chauhan D, Murthy V, Toumi M, Cadi-Soussi N. Humanistic burden in schizophrenia: a literature review. J Psychiatr Res. 2014 Jul;54:85-93. doi: 10.1016/j.jpsychires.2014.03.021. Epub 2014 Apr 4.
- 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.
- Vilela-Filho O, Ragazzo PC, Canedo D, Barreto US, Oliveira PM, Goulart LC, Reis MD, Campos TM. The impact of subcaudate tractotomy on delusions and hallucinations in psychotic patients. Surg Neurol Int. 2021 Sep 20;12:475. doi: 10.25259/SNI_599_2021. eCollection 2021.
- Vaernet K, Madsen A. Stereotaxic amygdalotomy and basofrontal tractotomy in psychotics with aggressive behaviour. J Neurol Neurosurg Psychiatry. 1970 Dec;33(6):858-63. doi: 10.1136/jnnp.33.6.858.
- Liu W, Hao Q, Zhan S, Li D, Pan S, Li Y, Lin G, Pan G, Mahyoub R, Sun B. Long-term follow-up of mri-guided bilateral anterior capsulotomy in patients with refractory schizophrenia. Stereotact Funct Neurosurg. 2014;92(3):145-52. doi: 10.1159/000360861. Epub 2014 May 7.
- Sun FT, Morrell MJ, Wharen RE Jr. Responsive cortical stimulation for the treatment of epilepsy. Neurotherapeutics. 2008 Jan;5(1):68-74. doi: 10.1016/j.nurt.2007.10.069.
- Motamedi GK, Lesser RP, Miglioretti DL, Mizuno-Matsumoto Y, Gordon B, Webber WR, Jackson DC, Sepkuty JP, Crone NE. Optimizing parameters for terminating cortical afterdischarges with pulse stimulation. Epilepsia. 2002 Aug;43(8):836-46. doi: 10.1046/j.1528-1157.2002.24901.x.
- Lesser RP, Kim SH, Beyderman L, Miglioretti DL, Webber WR, Bare M, Cysyk B, Krauss G, Gordon B. Brief bursts of pulse stimulation terminate afterdischarges caused by cortical stimulation. Neurology. 1999 Dec 10;53(9):2073-81. doi: 10.1212/wnl.53.9.2073.
- Benabid AL, Pollak P, Gervason C, Hoffmann D, Gao DM, Hommel M, Perret JE, de Rougemont J. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet. 1991 Feb 16;337(8738):403-6. doi: 10.1016/0140-6736(91)91175-t.
- Milosevic L, Kalia SK, Hodaie M, Lozano AM, Fasano A, Popovic MR, Hutchison WD. Neuronal inhibition and synaptic plasticity of basal ganglia neurons in Parkinson's disease. Brain. 2018 Jan 1;141(1):177-190. doi: 10.1093/brain/awx296.
- Lozano AM, Lipsman N. Probing and regulating dysfunctional circuits using deep brain stimulation. Neuron. 2013 Feb 6;77(3):406-24. doi: 10.1016/j.neuron.2013.01.020.
- Hoang KB, Turner DA. The Emerging Role of Biomarkers in Adaptive Modulation of Clinical Brain Stimulation. Neurosurgery. 2019 Sep 1;85(3):E430-E439. doi: 10.1093/neuros/nyz096.
- Dostrovsky JO, Lozano AM. Mechanisms of deep brain stimulation. Mov Disord. 2002;17 Suppl 3:S63-8. doi: 10.1002/mds.10143.
- Daalman K, Diederen KM, Hoekema L, van Lutterveld R, Sommer IE. Five year follow-up of non-psychotic adults with frequent auditory verbal hallucinations: are they still healthy? Psychol Med. 2016 Jul;46(9):1897-907. doi: 10.1017/S0033291716000386. Epub 2016 Mar 10.
- Brunelin J, Mondino M, Gassab L, Haesebaert F, Gaha L, Suaud-Chagny MF, Saoud M, Mechri A, Poulet E. Examining transcranial direct-current stimulation (tDCS) as a treatment for hallucinations in schizophrenia. Am J Psychiatry. 2012 Jul;169(7):719-24. doi: 10.1176/appi.ajp.2012.11071091.
- Miyamoto S, Miyake N, Jarskog LF, Fleischhacker WW, Lieberman JA. Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents. Mol Psychiatry. 2012 Dec;17(12):1206-27. doi: 10.1038/mp.2012.47. Epub 2012 May 15.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
17 de agosto de 2025
Conclusão Primária (Estimado)
31 de dezembro de 2028
Conclusão do estudo (Estimado)
31 de dezembro de 2028
Datas de inscrição no estudo
Enviado pela primeira vez
22 de junho de 2026
Enviado pela primeira vez que atendeu aos critérios de CQ
22 de junho de 2026
Primeira postagem (Real)
26 de junho de 2026
Atualizações de registro de estudo
Última Atualização Postada (Real)
26 de junho de 2026
Última atualização enviada que atendeu aos critérios de controle de qualidade
22 de junho de 2026
Última verificação
1 de julho de 2025
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- SEEG-Guided DBS for TRS
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
NÃO
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Não
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Não
produto fabricado e exportado dos EUA
Não
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