Enhancing Prefrontal Oscillations and Working Memory in Early-course Schizophrenia

NCT05102929 | Recruiting DMC FDA Device

• 2 other identifiers: STUDY200501941R01MH125816-01A1
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the effects of intermittent Theta Burst Stimulation (iTBS) on natural oscillatory frequency of the dorsolateral prefrontal cortex (DLPFC) and working memory in early-course schizophrenia (EC-SCZ). Transcranial magnetic stimulation (TMS) will be used to evoke oscillatory activity, and EEG will record the responses of EC-SCZ participants. A working memory task will also be incorporated in order to determine how DLPFC natural frequency (NF) is related to working memory performance. iTBS (active or sham) will be administered, then the oscillatory activity of DLPFC and working memory performance will be reassessed. The overarching goal is to determine whether iTBS can acutely enhance the oscillatory activity of the DLPFC and to evaluate the relationship between changes in the DLPFC and working memory performance.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (6)

• Change in dorsolateral prefrontal cortex natural frequency (DLPFC NF) following iTBS

  The difference in prefrontal natural frequency (DLPFC NF) between pre- and post- intermittent Theta Burst Stimulation (iTBS) in EC-SCZ patients

  baseline (pre iTBS), within one hour from iTBS

• Change in dorsolateral prefrontal event-related spectral perturbation (DLPFC ERSP) following iTBS

  The difference in prefrontal event-related spectral perturbation (DLPFC ERSP) between pre- and post- intermittent Theta Burst Stimulation (iTBS) in EC-SCZ patients

  baseline (pre iTBS), within one hour from iTBS

• Change in dorsolateral prefrontal inter-trial coherence (DLPFC ITC) following iTBS

  The difference in prefrontal inter trial coherence (DLPFC ITC) between pre- and post- intermittent Theta Burst Stimulation (iTBS) in EC-SCZ patients

  baseline (pre iTBS), within one hour from iTBS

• Change in AX-Continuous Performance Task Reaction Time (AX-CPT RT) following iTBS

  The difference in AX-Continuous Performance Task Reaction Time (AX-CPT RT) between pre- and post- intermittent Theta Burst Stimulation (iTBS) in EC-SCZ patients

  baseline (pre iTBS), within one hour from iTBS

• Change in AX-Continuous Performance Task Error Rate (AX-CPT ER) following iTBS

  The difference in AX-Continuous Performance Task Error Rate (AX-CPT ER) between pre- and post- intermittent Theta Burst Stimulation (iTBS) in EC-SCZ patients

  baseline (pre iTBS), within one hour from iTBS

• Change in AX-Continuous Performance Task d' context (AX-CPT d') following iTBS

  The difference in AX-Continuous Performance Task d' context (AX-CPT d') between pre- and post- intermittent Theta Burst Stimulation (iTBS) in EC-SCZ patients

  baseline (pre iTBS), within one hour from iTBS

Study Arms (2)

active, then sham Intermittent Theta Burst Stimulation (iTBS) over DLPFC

EXPERIMENTAL

This arm will first receive active iTBS stimulation and then sham iTBS over the left dorsolateral prefrontal cortex (DLPFC).

Device: active intermittent Theta Burst Stimulation (iTBS); Device: sham intermittent Theta Burst Stimulation (iTBS)

sham, then active intermittent Theta Burst Stimulation (iTBS) over DLPFC

EXPERIMENTAL

This arm will first receive sham iTBS (i.e., with the TMS coil in the placebo orientation) and then active iTBS stimulation over the left dorsolateral prefrontal cortex (DLPFC).

Device: active intermittent Theta Burst Stimulation (iTBS); Device: sham intermittent Theta Burst Stimulation (iTBS)

Interventions

sham intermittent Theta Burst Stimulation (iTBS) DEVICE

Sham TBS over the left DLPFC will be performed using a Cool-B65 A/P TMS coil, designed to support blinded clinical trials. Specifically, when the coil is placed in the "P" position (i.e. the "placebo" position), only a very small amount of current is induced in tissue, thus preventing the activation of cortical neurons.

active, then sham Intermittent Theta Burst Stimulation (iTBS) over DLPFC; sham, then active intermittent Theta Burst Stimulation (iTBS) over DLPFC

active intermittent Theta Burst Stimulation (iTBS) DEVICE

iTBS is a brief stimulation of a part of the brain with a magnetic field that passes through the scalp and skull safely. It is FDA-approved as a treatment for psychological conditions including depression; however, this device is not approved for the treatment of adults with patients with schizophrenia. This research study is using iTBS off label in SCZ patients to examine research questions.

Also known as: Transcranial Magnetic Stimulation

active, then sham Intermittent Theta Burst Stimulation (iTBS) over DLPFC; sham, then active intermittent Theta Burst Stimulation (iTBS) over DLPFC

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• ages 18-40 years
• DSM diagnoses of Schizophrenia Spectrum Axis I disorders
• a duration of less than three years from beginning of psychosis, defined by report of symptoms and/or history of treatment, based on clinical guidelines employed in our UPMC psychoses clinics in Pittsburgh.

You may not qualify if:

• DSM intellectual developmental disorder
• significant head injury
• medical illness affecting brain structure or function
• significant neurologic disorder (e.g. seizure disorder)
• personal history or family history of epilepsy
• inability to provide informed consent
• concussion with loss of consciousness (LOC) greater than 10 minutes
• history of electroconvulsive therapy
• diabetes with associated seizures, loss of sensation/weakness in arms or legs, or momentary LOC
• pregnancy or postpartum (\<6 weeks after delivery or miscarriage), as determined by self-report
• a psychotic illness with a temporal relation to substance use or head injury.
• current or past co-morbidity for alcohol or psychoactive substance dependence
• substance abuse, other than cannabis and/or alcohol, within the past one year

Sponsors & Collaborators

• Fabio Ferrarelli: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

MeSH Terms

Conditions

Schizophrenia

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Fabio Ferrarelli, MD, PhD

  University of Pittsbrugh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sabine Janssen

CONTACT

412-246-6114; janssensa@upmc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 20, 2021
• First Posted: November 2, 2021
• Study Start: November 5, 2021
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: February 9, 2026

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)