Accelerated Transcranial Magnetic Stimulation for People With Schizophrenia Treated With Clozapine

Accelerated Neuromodulation of Prefrontal Circuitry During Clozapine Treatment

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.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Schizoaffective Disorder
• Intervention / Treatment: Device: sham stimulation; Device: transcranial magnetic stimulation

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tori Blazinski; Phone Number: 412-246-5618; Email: blazinskit2@upmc.edu
• Study Contact Backup: Name: Deepak Sarpal; Email: sarpaldk@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • UPMC Western Psychiatric Hospital/University of Pittsburgh
      • Contact: Tori Blazinski; Email: blazinskit2@upmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: iTBS, then Sham	Device: sham stimulation; sham delivery of transcranial magnetic stimulation; Device: transcranial magnetic stimulation; accelerated intermittent theta burst stimulation
Experimental: Sham, then iTBS	Device: sham stimulation; sham delivery of transcranial magnetic stimulation; Device: transcranial magnetic stimulation; accelerated intermittent theta burst stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in brain functional connectivity within the prefrontal cortex	Examine changes in left dorsolateral prefrontal cortex-basal forebrain functional connectivity following adjunctive accelerated intermittent theta burst stimulation (iTBS)	1 hour
change in activation of the working memory network	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	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
explore change in functional magnetic resonance imaging (fMRI) measures versus plasma n-desmethylclozapine/clozapine ratios	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.	1 month

Collaborators and Investigators

• Sponsor: Deepak Sarpal
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Deepak K Sarpal, M.D., University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: August 8, 2023
• First Submitted That Met QC Criteria: August 14, 2023
• First Posted (Actual): August 21, 2023

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders
• Other Study ID Numbers: STUDY23050056; R21MH134128 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: de-identified individual participant data to the National Institute of Mental Health (NIMH) data archive

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No