Accelerated Transcranial Magnetic Stimulation for People With Schizophrenia Treated With Clozapine

Schizophrenia Clinical Trial

Official title:

Accelerated Neuromodulation of Prefrontal Circuitry During Clozapine Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06003036
• Other study ID #: STUDY23050056
• Secondary ID: R21MH134128
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2023
• Est. completion date: September 2025

Study information

• Verified date: February 2024
• Source: University of Pittsburgh
• Contact: Tori Blazinski
• Phone: 412-246-5618
• Email: blazinskit2[@]upmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia

Intervention

Device:
• sham stimulation
sham delivery of transcranial magnetic stimulation
• transcranial magnetic stimulation
accelerated intermittent theta burst stimulation

Locations

Country	Name	City	State
United States	UPMC Western Psychiatric Hospital/University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Deepak Sarpal	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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