Medial-prefrontal Enhancement During Schizophrenia Systems Imaging

NCT04807530 | Recruiting FDA Device

• 2 other identifiers: 1228971R01MH122897-01
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized controlled trial in healthy controls (HC) and patients with schizophrenia (SZ) aims to examine 1) the underlying cognitive and neural cause of self-agency deficits in SZ; 2) the responsiveness to a novel navigated repetitive transcranial magnetic stimulation (nrTMS) target in the medial/superior prefrontal cortex (mPFC); and 3) how modulation of mPFC activity impacts the larger self-agency network to mediate changes in self-agency judgments. Our overall hypothesis is that increased mPFC excitability by active high-frequency nrTMS in HC and SZ will induce behavioral improvements in self-agency and neural changes in the larger self-agency network that will generalize to improvements in overall cognition, symptoms and daily functioning, and will likely lead to the development of new effective neuromodulation therapies in patients with schizophrenia.

Conditions

Schizophrenia

Keywords

Schizophrenia; Transcranial Magnetic Stimulation; Prefrontal Cortex; Self-Agency; Reality Monitoring

Outcome Measures

Primary Outcomes (4)

• Self-Agency Behavioral Change during Reality Monitoring after TMS vs Baseline (metrics of accuracy)

  Change in retrieval accuracy of self-generated information during reality monitoring task from baseline to post-TMS. No scales used.

  From baseline, to immediately after TMS, up to 1 week

• Self-Agency Behavioral Change during Speech Monitoring after TMS vs Baseline (metrics of speech perturbation units)

  Change in speech corrective responses during altered vs. unaltered auditory feedback, measured in units of speech perturbation (cents) from baseline to post-TMS. No scales used.

  From baseline, to immediately after TMS, up to 1 week

• MEGI Neural Activity Change related to Self-Agency during Reality Monitoring after TMS vs Baseline (metrics of neural beta activation units)

  Whole-brain neural activity change related to self-agency by contrasting oscillatory activity during encoding and retrieval of self-generated information with encoding and retrieval of externally-derived information (with focus on mPFC and parietal cortices as our region-of-interest (ROI)), measured in beta weights neural signal change from baseline to post-TMS. No scales used.

  From baseline, to immediately after TMS, up to 1 week

• MEGI Neural Activity Change related to Self-Agency during Speech Monitoring after TMS vs Baseline (metrics of neural beta activation units)

  Whole-brain neural activity related to self-agency by contrasting oscillatory activity related to speech onset during altered auditory feedback with activity related to speech onset during unaltered auditory feedback (with focus on mPFC and parietal cortices for ROI analyses) measured in beta weights neural signal change from baseline to post-TMS. No scales used.

  From baseline, to immediately after TMS, up to 1 week

Secondary Outcomes (3)

• Cognition Change after TMS vs Baseline (metrics units of accuracy and speed of processing)

  From baseline to immediate and distal time points after TMS, up to 4 weeks

• Clinical Symptom Change after TMS vs Baseline (metrics units of severity)

  From baseline to immediate and distal time points after TMS, up to 4 weeks

• Daily Functioning Change after TMS vs. Baseline (metrics of functioning)

  From baseline to immediate and distal time points after TMS, up to 4 weeks

Study Arms (2)

Medial/Superior Prefrontal TMS

ACTIVE COMPARATOR

10 Hz High frequency TMS applied to the mPFC

Device: TMS

Posterior Parietal TMS

PLACEBO COMPARATOR

10 Hz high frequency TMS applied to the posterior parietal cortex

Device: TMS

Interventions

TMS DEVICE

The investigators will use the NEXSTIM NAVIGATED BRAIN STIMULATION (NBS) SYSTEM to apply 10 Hz nrTMS to healthy controls (HC) and schizophrenia patients (SZ)

Medial/Superior Prefrontal TMS; Posterior Parietal TMS

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• All Subjects:
• Good general physical health
• English is first language
• No neurological disorder
• Meets MRI criteria
• No current alcohol or substance use disorder
• Schizophrenia participants:
• Schizophrenia diagnosis of any illness duration,
• Clinical stability, defined as 12 weeks outpatient status and 4 weeks low to moderate dose of antipsychotic medication (\<1000 mg. chlorpromazine equivalents), plus stable doses of all other psychotropic medications

You may not qualify if:

• All Subjects:
• Implanted metallic parts of implanted electronic devices
• Pregnant or trying to become pregnant
• Any condition that would prevent the subject from giving voluntary informed consent
• Scalp wounds or infections
• Claustrophobia precluding MRI
• Ongoing seizures
• Neurological disorder

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

UCSF

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Karuna Subramaniam, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karuna Subramaniam, Ph.D

CONTACT

415-221-4810; karuna.subramaniam@ucsf.edu

Miriam Mathew, PhD

CONTACT

miriam.mathew@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Participants and care providers and all clinical outcomes assessors will be blinded as to whether participants will receive the active nrTMS or control nrTMS.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The investigators propose a longitudinal randomized controlled trial (RCT) in which 80 SZ and 80 HC are randomly assigned to either active high-frequency 10Hz nrTMS to increase activity in medial/superior prefrontal cortex (mPFC) or a control posterior parietal site. The investigators assess durability and generalizability of how active 10Hz nrTMS modulation of mPFC activity in HC and SZ causally induces neural network changes that mediate behavioral changes in self-agency to impact overall cognition, clinical and daily functioning, compared to the control parietal site and baseline.

Study Record Dates

• First Submitted: March 17, 2021
• First Posted: March 19, 2021
• Study Start: November 12, 2020
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: August 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The investigators aim to complete all data analyses by end of 2025-2026, when the complete, and all deidentified data will be available for sharing

Locations

US (1)