SEEG-Guided DBS for Schizophrenia
2026年6月22日 更新者：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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (推定)
46
段階
- 適用できない
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Shuo Ma, PhD
- 電話番号：86+15000838003
- メール：ms13144@rjh.com.cn
研究場所
-
-
Shanghai Municipality
-
Shanghai、Shanghai Municipality、中国、200025
- 募集
- Ruijin Hospital, Shanghai Jiaotong University School of Medicine
-
コンタクト：
- Shuo Ma, PhD
- 電話番号：86+15000838003
- メール：ms13144@rjh.com.cn
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
健康ボランティアの受け入れ
いいえ
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ：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.
|
|
プラセボコンパレーター：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.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Reduction Rate of PANSS Positive Subscale or SAPS
時間枠：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.
|
Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Reduction Rate of Auditory Hallucinations (Assessed by PSYRATS-AH)
時間枠：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.
|
Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
|
|
Reduction Rate of Delusions (Assessed by PSYRATS-D)
時間枠：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.
|
Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
|
|
Reduction Rate of Depressive Symptoms (Assessed by HAMD)
時間枠：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.
|
Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
|
|
Reduction Rate of Anxiety Symptoms (Assessed by HAMA)
時間枠：Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
|
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.
|
Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
|
|
Improvement Rate of Cognitive Function (Assessed by MoCA)
時間枠：Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
|
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.
|
Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2025年8月17日
一次修了 (推定)
2028年12月31日
研究の完了 (推定)
2028年12月31日
試験登録日
最初に提出
2026年6月22日
QC基準を満たした最初の提出物
2026年6月22日
最初の投稿 (実際)
2026年6月26日
学習記録の更新
投稿された最後の更新 (実際)
2026年6月26日
QC基準を満たした最後の更新が送信されました
2026年6月22日
最終確認日
2025年7月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。