SEEG-Guided DBS for Schizophrenia

NCT07671261 | Recruiting

• 1 other identifier: SEEG-Guided DBS for TRS
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Schizophrenia Disorders; Schizo Affective Disorder

Keywords

Schizophrenia; Stereoelectroencephalography; Neuroimaging; deep brain stimulation

Outcome Measures

Primary Outcomes (1)

• Reduction Rate of PANSS Positive Subscale or SAPS

  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.

Secondary Outcomes (5)

• Reduction Rate of Auditory Hallucinations (Assessed by PSYRATS-AH)

  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)

  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)

  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)

  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)

  Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation.

Study Arms (2)

Stim ON-OFF

ACTIVE COMPARATOR

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.

Procedure: SEEG implantation; Device: Deep brain stimulation

Stim OFF-ON

PLACEBO COMPARATOR

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.

Procedure: SEEG implantation; Device: Deep brain stimulation

Interventions

SEEG implantation PROCEDURE

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.

Stim OFF-ON; Stim ON-OFF

Deep brain stimulation DEVICE

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.

Stim OFF-ON; Stim ON-OFF

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital, Shanghai JiaoTong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

Related Publications (18)

• 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.

  PMID: 34621590 BACKGROUND

• 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.

  PMID: 5531905 BACKGROUND

• 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.

  PMID: 24818571 BACKGROUND

• 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.

  PMID: 34608328 BACKGROUND

• 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.

  PMID: 15748841 BACKGROUND

• 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.

  PMID: 18164485 BACKGROUND

• 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.

  PMID: 12181002 BACKGROUND

• 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.

  PMID: 10599784 BACKGROUND

• 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.

  PMID: 9770557 BACKGROUND

• 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.

  PMID: 1671433 BACKGROUND

• 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.

  PMID: 29236966 BACKGROUND

• 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.

  PMID: 23395370 BACKGROUND

• 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.

  PMID: 30957145 BACKGROUND

• Dostrovsky JO, Lozano AM. Mechanisms of deep brain stimulation. Mov Disord. 2002;17 Suppl 3:S63-8. doi: 10.1002/mds.10143.

  PMID: 11948756 BACKGROUND

• 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.

  PMID: 26961499 BACKGROUND

• 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.

  PMID: 22581236 BACKGROUND

• 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.

  PMID: 22584864 BACKGROUND

• 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.

  PMID: 24795289 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Central Study Contacts

Shuo Ma, PhD

CONTACT

86+15000838003; ms13144@rjh.com.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: June 22, 2026
• First Posted: June 26, 2026
• Study Start: August 17, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 26, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)