Accelerated Transcranial Magnetic Stimulation for People With Schizophrenia Treated With Clozapine

• Sponsor: Deepak Sarpal (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06003036
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 30
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 24
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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 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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizoaffective Disorder	Device: sham stimulation; Device: transcranial magnetic stimulation	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: Accelerated Neuromodulation of Prefrontal Circuitry During Clozapine Treatment
• Anticipated Study Start Date: Sep 1, 2023
• Anticipated Primary Completion Date: Jun 1, 2025
• Anticipated Study Completion Date: Sep 1, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 iTBS

2. change in activation of the working memory network [1 hour]

   Examine whether accelerated iTBS is associated with fMRI-based changes in activation of the working memory network during AX-CPT task engagement

Secondary Outcome Measures

1. explore change in fMRI-based 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. A current DSM defined diagnosis of schizophrenia or schizoaffective disorder

2. age 18-50 years

3. at least 4 months of CLZ 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 MR imaging (e.g., a pacemaker)

7. the Structured Clinical Interview for DSM 5 (SCID)-verified moderate or severe substance use disorder, including alcohol use disorder, to mitigate confounding by substance use comorbidity

8. seizure disorder or prior history of seizures on clozapine

9. patients taking both Wellbutrin and clozapine

10. prior issues with iTBS/TMS administration

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UPMC Western Psychiatric Hospital/University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213

Sponsors and Collaborators

• Deepak Sarpal
• National Institute of Mental Health (NIMH)

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Deepak Sarpal, Assistant Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT06003036
• Other Study ID Numbers: STUDY23050056; R21MH134128
• First Posted: Aug 21, 2023
• Last Update Posted: Aug 21, 2023
• Last Verified: Aug 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Additional relevant MeSH terms: Schizophrenia; Psychotic Disorders

Study Results

No Results Posted as of Aug 21, 2023