Brain Stimulation to the Hippocampus in Schizophrenia

Stanford University

Status: Begins enrollment in 2 months

Conditions: Mental Disorder; Schizophrenia Disorders; Psychotic Disorder

Treatments: Device: TMS sham; Device: TMS; Device: Intracranial electrodes

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07010614

340902

Details and patient eligibility

About

Schizophrenia - marked by delusions, hallucinations, and cognitive deficits - causes the most disability of any mental health condition, but existing treatments have significant side effect burden and are often ineffective. Disordered neural activity in the hippocampus likely contributes to schizophrenia symptoms, but to develop better therapies we need to understand whether hippocampal activity in schizophrenia can be systematically affected by non-invasive brain stimulation techniques like transcranial magnetic stimulation (TMS). This proposal will investigate the use of connectivity-guided theta burst brain stimulation to specifically target hippocampal function in schizophrenia, offering insights into fundamental hippocampal processes, schizophrenia pathophysiology, and potential avenues to use brain stimulation as a therapeutic tool in this devastating illness.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Men and women, ages 18 to 65 years
• Medically intractable epilepsy requiring phase II monitoring (intracranial EEG arms only)
• DSM-V diagnosis of schizophrenia spectrum Axis I disorders including delusional disorder, brief psychotic disorder, schizophreniform disorder, schizophrenia, schizoaffective disorder (non-invasive TMS-EEG arms only).
• Must have intellectual capacity to ensure adequate comprehension of the study and potential risks involved in order to provide informed consent
• No current or history of major neurological disorders other than epilepsy.

Exclusion criteria

• DSM5 diagnosis of intellectual disability
• Significant head injury
• Active suicidal ideation or history of suicide attempt within the past 1 year.
• Medical illness affecting brain structure or function, or other uncontrolled or unstable medical condition.
• Pregnancy or postpartum (<6 weeks after delivery or miscarriage)
• Inability to provide informed consent
• Active substance abuse other than alcohol or cannabis within the past 1 year
• Psychotic illness with a temporal relation to substance use or head injury
• Those with a contraindication for MRIs or TMS (e.g. implanted metal).

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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60 participants in 4 patient groups

TBS via direct electrical stimulation

Active Comparator group

Description:

Intracranial electrodes will be used for the delivery of invasive electrical brain stimulation in a theta burst (TBS) pattern.

Treatment:

Device: Intracranial electrodes

TBS via transcranial magnetic stimulation

Active Comparator group

Description:

TMS will be used for the delivery of noninvasive brain stimulation in a theta burst (TBS) pattern.

Treatment:

Device: TMS

Sham TBS via direct electrical stimulation

Sham Comparator group

Description:

Intracranial electrodes will be used for the delivery of sham invasive brain stimulation (time periods where electrical current is paused).

Treatment:

Device: Intracranial electrodes

Sham TBS via transcranial magnetic stimulation

Sham Comparator group

Description:

TMS will be used for the delivery of sham noninvasive brain stimulation (active side of coil turned away from the brain).

Treatment:

Device: TMS sham