Hippocampus DBS in Treatment-resistant Schizophrenia

Sponsor
Shanghai Mental Health Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT05694000
Collaborator
Huashan Hospital (Other)
6
1
2
37
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Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Device: On-Stimulation
  • Device: Off-Stimulation
N/A

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 Design

Study Type:
Interventional
Anticipated Enrollment :
6 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Deep Brain Stimulation of the Ventral Hippocampus in Treatment-resistant Schizophrenia: Exploring the Glutamatergic/GABAergic Mechanisms
Actual Study Start Date :
Nov 1, 2022
Anticipated Primary Completion Date :
Dec 1, 2024
Anticipated Study Completion Date :
Dec 1, 2025

Arms and Interventions

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".

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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

  2. 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

  3. 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

  4. 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

Other Outcome Measures

  1. Adverse events (AEs) [Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks]

    Any unexpected medical problem that may happen during DBS treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Shanghai Mental Health Center Shanghai Shanghai China 200030

Sponsors and Collaborators

  • Shanghai Mental Health Center
  • Huashan Hospital

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Dengtang LIU, Chief Psychiatrist and Professor, Shanghai Mental Health Center
ClinicalTrials.gov Identifier:
NCT05694000
Other Study ID Numbers:
  • 82171496
First Posted:
Jan 23, 2023
Last Update Posted:
Jan 23, 2023
Last Verified:
Jan 1, 2023
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 23, 2023