Hippocampus DBS in Treatment-resistant Schizophrenia

Treatment-resistant Schizophrenia Clinical Trial

Official title:

Deep Brain Stimulation of the Ventral Hippocampus in Treatment-resistant Schizophrenia: Exploring the Glutamatergic/GABAergic Mechanisms

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05694000
• Other study ID #: 82171496
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2022
• Est. completion date: December 2025

Study information

• Verified date: January 2023
• Source: Shanghai Mental Health Center
• Contact: Dengtang Liu
• Phone: 021-64387986
• Email: liudengtang[@]smhc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Schizophrenia
• Treatment-resistant Schizophrenia

Intervention

Device:
• On-Stimulation
The surgical electrode implanted in hippocampus by a pulse generating device is "on".
• Off-Stimulation
The surgical electrode implanted in hippocampus by a pulse generating device is "off".

Locations

Country	Name	City	State
China	Shanghai Mental Health Center	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Mental Health Center	Huashan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events (AEs)	Any unexpected medical problem that may happen during DBS treatment	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
Primary	Positive and Negative Syndrome Scale for Schizophrenia (PANSS)	Scale to assess changes in clinical symptoms; response to DBS is defined as a 20% reduction from baseline in PANSS score	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
Secondary	Clinical Global Impression-Schizophrenia (CGI-SCH) Scale	Scale to assess changes in symptoms' severity, global improvement or change	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
Secondary	Clinician-Rated Dimensions of Psychosis Symptom severity (CRDPS) Scale	Scale to assess different dimensions and severity of symptoms	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
Secondary	The Chinese version of Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery	Battery of neuropsychological tests to assess changes in cognition	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
Secondary	Cerebral metabolism(PET-CT scans)	Assessment of changes in metabolic levels of glutamate, GABA and dopamine in the whole brain using PET-CT	Baseline, 24 weeks, 48 weeks