Back to resultsHippocampus DBS in Treatment-resistant Schizophrenia
Primary Purpose
Treatment-resistant Schizophrenia
Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
On-Stimulation
Off-Stimulation
Sponsored by
About this trial
This is an interventional treatment trial for Treatment-resistant Schizophrenia
Eligibility Criteria
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: Persistence of positive symptoms which have not responded to appropriate treatments for at least 2 years. Inadequate response from adequate trials of two different classes of antipsychotic drugs (not including clozapine), at least 8 weeks. Inadequate response from adequate trial of clozapine, at least 3 months, or unable to tolerate clozapine because of intolerable side effects. 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
Sites / Locations
- Shanghai Mental Health CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
On-Stimulation
Off-Stimulation
Arm Description
Disease condition is assessed with stimulation turned "on".
Disease condition is assessed with stimulation turned "off".
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Clinical Global Impression-Schizophrenia (CGI-SCH) Scale
Scale to assess changes in symptoms' severity, global improvement or change
Clinician-Rated Dimensions of Psychosis Symptom severity (CRDPS) Scale
Scale to assess different dimensions and severity of symptoms
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
Cerebral metabolism(PET-CT scans)
Assessment of changes in metabolic levels of glutamate, GABA and dopamine in the whole brain using PET-CT
Full Information
NCT ID
NCT05694000
First Posted
December 9, 2022
Last Updated
January 19, 2023
Sponsor
Shanghai Mental Health Center
Collaborators
Huashan Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05694000
Brief Title
Hippocampus DBS in Treatment-resistant Schizophrenia
Official Title
Deep Brain Stimulation of the Ventral Hippocampus in Treatment-resistant Schizophrenia: Exploring the Glutamatergic/GABAergic Mechanisms
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2022 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Mental Health Center
Collaborators
Huashan Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment-resistant Schizophrenia
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
6 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
On-Stimulation
Arm Type
Active Comparator
Arm Description
Disease condition is assessed with stimulation turned "on".
Arm Title
Off-Stimulation
Arm Type
Placebo Comparator
Arm Description
Disease condition is assessed with stimulation turned "off".
Intervention Type
Device
Intervention Name(s)
On-Stimulation
Intervention Description
The surgical electrode implanted in hippocampus by a pulse generating device is "on".
Intervention Type
Device
Intervention Name(s)
Off-Stimulation
Intervention Description
The surgical electrode implanted in hippocampus by a pulse generating device is "off".
Primary Outcome Measure Information:
Title
Positive and Negative Syndrome Scale for Schizophrenia (PANSS)
Description
Scale to assess changes in clinical symptoms; response to DBS is defined as a 20% reduction from baseline in PANSS score
Time Frame
Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
Secondary Outcome Measure Information:
Title
Clinical Global Impression-Schizophrenia (CGI-SCH) Scale
Description
Scale to assess changes in symptoms' severity, global improvement or change
Time Frame
Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
Title
Clinician-Rated Dimensions of Psychosis Symptom severity (CRDPS) Scale
Description
Scale to assess different dimensions and severity of symptoms
Time Frame
Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
Title
The Chinese version of Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery
Description
Battery of neuropsychological tests to assess changes in cognition
Time Frame
Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
Title
Cerebral metabolism(PET-CT scans)
Description
Assessment of changes in metabolic levels of glutamate, GABA and dopamine in the whole brain using PET-CT
Time Frame
Baseline, 24 weeks, 48 weeks
Other Pre-specified Outcome Measures:
Title
Adverse events (AEs)
Description
Any unexpected medical problem that may happen during DBS treatment
Time Frame
Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
Persistence of positive symptoms which have not responded to appropriate treatments for at least 2 years.
Inadequate response from adequate trials of two different classes of antipsychotic drugs (not including clozapine), at least 8 weeks.
Inadequate response from adequate trial of clozapine, at least 3 months, or unable to tolerate clozapine because of intolerable side effects.
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dengtang Liu
Phone
021-64387986
Email
liudengtang@smhc.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dengtang Liu
Organizational Affiliation
liudengtang@smhc.org.cn
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Mental Health Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200030
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dengtang LIU
Phone
18017311138
Email
erliu110@126.com
12. IPD Sharing Statement
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Hippocampus DBS in Treatment-resistant Schizophrenia
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