Accelerated Transcranial Magnetic Stimulation for People With Schizophrenia Treated With Clozapine

August 5, 2026 updated by: Deepak K. Sarpal, M.D.

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

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

30

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 Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC Western Psychiatric Hospital/University of Pittsburgh

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

  • Adult
  • Older 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 18-65 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

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

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
Time Frame: 1 hour
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
Time Frame: 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
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
Time Frame: 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.
1 month

Collaborators and Investigators

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

Sponsor

Deepak K. Sarpal, M.D.

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Deepak K Sarpal, M.D., University of Pittsburgh

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)

December 1, 2023

Primary Completion (Actual)

January 12, 2026

Study Completion (Actual)

January 12, 2026

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)

August 10, 2026

Last Update Submitted That Met QC Criteria

August 5, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

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

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.

Subscribe