Accelerated Transcranial Magnetic Stimulation for People with Schizophrenia Treated with Clozapine

Not Applicable

Recruiting

• Conditions: Schizoaffective Disorder; Schizophrenia
• Interventions: Device: sham stimulation; Device: transcranial magnetic stimulation

• Registration Number: NCT06003036
• Lead Sponsor: Deepak K. Sarpal, M.D.

Brief Summary

In this study, the investigators will examine whether a type of repetitive transcranial magnetic stimulation called accelerated intermittent theta burst stimulation (iTBS) can augment neurocognition in individuals who receive treatment with clozapine. Following a baseline evaluation and magnetic resonance imaging (MRI), participants will undergo a session of iTBS +MRI and session of sham delivery + MRI. The order for these sessions will be blinded and randomized. The investigators predict that accelerated iTBS will enhance neurocognition relative to sham delivery.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-08-08
• Study First Submitted QC: 2023-08-14
• Study First Posted: 2023-08-21
• Study Start: 2023-12-01
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-25
• Last Update Posted: 2025-02-28
• Primary Completion: 2025-06
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. A current Diagnostic and Statistical Manual of Mental Disorders 5 (DSM 5)-defined diagnosis of schizophrenia or schizoaffective disorder
2. age 18-50 years
3. at least 4 months of clozapine treatment
4. history of at least 2 failed antipsychotic trials
5. competency and willingness to sign informed consent
6. A clinically optimized dosage of clozapine, unchanged for at least 1 month, with a minimum of 150 mg/day

Exclusion Criteria

1. Serious neurologic or medical condition/treatment that impacts the brain
2. a significant risk of suicidal or homicidal behavior
3. cognitive or language limitations, or any other factor that would preclude subjects providing informed consent
4. pregnancy or postpartum (<6 weeks after delivery or miscarriage)
5. history of treatment with electroconvulsive therapy
6. contraindications for magnetic resonance imaging (e.g., a pacemaker)
7. Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders 5 (DSM 5)-verified moderate or severe substance use disorder, including alcohol use disorder
8. seizure disorder or prior history of seizures on clozapine
9. patients taking both bupropion and clozapine
10. prior issues with intermittent theta burst stimulation/transcranial magnetic stimulation administration

Concomitant treatment with serotonin and norepinephrine reuptake inhibitors will be examined on a case-by-case basis.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
iTBS, then Sham	transcranial magnetic stimulation	-
Sham, then iTBS	transcranial magnetic stimulation	-
iTBS, then Sham	sham stimulation	-
Sham, then iTBS	sham stimulation	-

Primary Outcome Measures

Name	Time	Method
change in activation of the working memory network	1 hour	Examine whether accelerated intermittent theta burst stimulation (iTBS) is associated with functional magnetic resonance imaging (fMRI)-based changes in activation of the working memory network during AX-continuous performance task engagement
change in brain functional connectivity within the prefrontal cortex	1 hour	Examine changes in left dorsolateral prefrontal cortex-basal forebrain functional connectivity following adjunctive accelerated intermittent theta burst stimulation (iTBS)

Secondary Outcome Measures

Name	Time	Method
explore change in functional magnetic resonance imaging (fMRI) measures versus plasma n-desmethylclozapine/clozapine ratios	1 month	In exploratory analyses we will compare change in dorsolateral prefrontal cortex-basal forebrain functional connectivity and change in working memory network activation in relation to plasma n-desmethylclozapine/clozapine ratios.

Trial Locations

Locations (1)

UPMC Western Psychiatric Hospital/University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States