Hippocampus DBS in Treatment-resistant Schizophrenia

January 19, 2023 updated by: Dengtang LIU, Shanghai Mental Health Center

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

6

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200030
        • Recruiting
        • Shanghai Mental Health Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: On-Stimulation
Disease condition is assessed with stimulation turned "on".
Device: On-Stimulation
The surgical electrode implanted in hippocampus by a pulse generating device is "on".
Placebo Comparator: Off-Stimulation
Disease condition is assessed with stimulation turned "off".
Device: Off-Stimulation
The surgical electrode implanted in hippocampus by a pulse generating device is "off".

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Positive and Negative Syndrome Scale for Schizophrenia (PANSS)
Time Frame: 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
Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events (AEs)
Time Frame: Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
Any unexpected medical problem that may happen during DBS treatment
Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Mental Health Center

Collaborators

Huashan Hospital

Investigators

  • Principal Investigator: Dengtang Liu, liudengtang@smhc.org.cn

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2022

Primary Completion (Anticipated)

December 1, 2024

Study Completion (Anticipated)

December 1, 2025

Study Registration Dates

First Submitted

December 9, 2022

First Submitted That Met QC Criteria

January 19, 2023

First Posted (Actual)

January 23, 2023

Study Record Updates

Last Update Posted (Actual)

January 23, 2023

Last Update Submitted That Met QC Criteria

January 19, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 82171496

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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