Hippocampus DBS in Treatment-resistant Schizophrenia

Not Applicable

Recruiting

• Conditions: Treatment-resistant Schizophrenia
• Interventions: Device: On-Stimulation; Device: Off-Stimulation

• Registration Number: NCT05694000
• Lead Sponsor: Shanghai Mental Health Center

Brief Summary

The goal of this clinical trial is to assess the efficacy and safety of hippocampus-targeted deep brain stimulation (DBS) in treatment-resistant schizophrenia. The main question it aims to answer are:

* whether patients with treatment-resistant schizophrenia can benefit from hippocampus-targeted DBS;

* what is the neural and electrophysiological mechanism underlying the treatment effect of hippocampus-targeted DBS.

Detailed Description

The first phase of the study will consist of DBS surgery. Participants will receive electrodes implantation in bilateral ventral hippocampus. Continuous stimulation will be applied to optimize and individualize the stimulus parameters. This period is anticipated between 3 and 6 months.

The next phase will consist of the crossover study. Patients who respond to DBS will be randomly assigned to two groups, for a period of 3 months: on stimulation group and off stimulation group. Patients will then be crossed over to the other group for a further 3 months.

Participants will receive PET-CT, clinical assessment and cognitive tests at the main study points to evaluate treatment efficacy and patient tolerance, and to reveal the underlying mechanism of the treatment effect of DBS.

Study Timeline

• Study Start: 2022-11-01
• Study First Submitted: 2022-12-09
• Status Verified: 2023-01
• Study First Submitted QC: 2023-01-19
• Last Update Submitted: 2023-01-19
• Study First Posted: 2023-01-23
• Last Update Posted: 2023-01-23
• Primary Completion: 2024-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

• Male or female aged between 18 and 55 years.

• Having a diagnosis of schizophrenia according to DSM-IV criteria

• Having a chronic, recurrent course of disease with a five-year minimum duration

• Determined to be treatment-resistant as demonstrated by:

  1. Persistence of positive symptoms which have not responded to appropriate treatments for at least 2 years.
  2. Inadequate response from adequate trials of two different classes of antipsychotic drugs (not including clozapine), at least 8 weeks.
  3. Inadequate response from adequate trial of clozapine, at least 3 months, or unable to tolerate clozapine because of intolerable side effects.
  4. Presence of persistent positive symptom defined as i) requiring a score of 4 (moderate) or more on at least 2 of the next PANSS items: delusions, conceptual disorganization, hallucinatory behavior, suspiciousness and unusual thought content; or as ii) requiring a score of 6 (severe) or more on at least 1 of the above PANSS items.

• Maintaining stable pharmacological treatment for two months preceding screening visit.

• Informed consent

Exclusion Criteria

• Neurological disease
• Severe physical illness
• Contraindications to neurosurgery, MRI or PET-CT;
• Substance abuse or dependence
• Mental retardation
• Female patients who are pregnant or breastfeeding
• Severe suicide risk and tendencies

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
On-Stimulation	On-Stimulation	Disease condition is assessed with stimulation turned "on".
Off-Stimulation	Off-Stimulation	Disease condition is assessed with stimulation turned "off".

Primary Outcome Measures

Name	Time	Method
Positive and Negative Syndrome Scale for Schizophrenia (PANSS)	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks	Scale to assess changes in clinical symptoms; response to DBS is defined as a 20% reduction from baseline in PANSS score

Secondary Outcome Measures

Name	Time	Method
The Chinese version of Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks	Battery of neuropsychological tests to assess changes in cognition
Clinician-Rated Dimensions of Psychosis Symptom severity (CRDPS) Scale	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks	Scale to assess different dimensions and severity of symptoms
Cerebral metabolism(PET-CT scans)	Baseline, 24 weeks, 48 weeks	Assessment of changes in metabolic levels of glutamate, GABA and dopamine in the whole brain using PET-CT
Clinical Global Impression-Schizophrenia (CGI-SCH) Scale	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks	Scale to assess changes in symptoms' severity, global improvement or change

Trial Locations

Locations (1)

Shanghai Mental Health Center; 🇨🇳 Shanghai, Shanghai, China