SchizophreniaMESSINCT04807530
Medial-prefrontal Enhancement During Schizophrenia Systems Imaging
A study testing TMS in people with Schizophrenia, run by University of California, San Francisco at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- TMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Nov 2020to 30 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- All Subjects:
- Good general physical health
- English is first language
- No neurological disorder
- Meets MRI criteria
- No current alcohol or substance use disorder
Show all 9Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Miriam Mathew, PhD contact
United States1 site, 1 recruiting
- Recruiting
UCSF
San Francisco, California, 94143
Miriam Mathew, PhD, miriam.mathew@ucsf.edu
About this study
Official title: Causal Role of Medial Prefrontal Neural Activity in Self-Agency in Schizophrenia
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.
Read the detailed description
This longitudinal mechanistic randomized controlled trial in patients with schizophrenia (SZ) and matched healthy controls (HC) examines the underlying cause of self-agency deficits in SZ and their responsiveness to navigated repetitive transcranial magnetic stimulation (nrTMS) of the medial prefrontal cortex. Using a multimodal neuroimaging approach that combines structural MRI with functional magnetoencephalography imaging (MEGI) and nrTMS that is integrated with cognitive and clinical assessments, this research provides an unprecedented rigorous assessment of the neural and cognitive basis of self-agency and its modulation by nrTMS, using two distinct and validated paradigms involving speech monitoring (pitch perturbation) and reality monitoring.
Subjects will first be assessed for 1 week for diagnostic inclusion criteria and eligibility assessment. They will complete baseline assessments (i.e., cognitive, clinical and daily functioning assessments, structural MRI, and MEGI scans while they perform reality and speech monitoring tasks). After baseline assessments, 80 SZ and 80 age, gender, and education-matched HC will be randomly assigned to either active 10Hz nrTMS targeting mPFC (40HC and 40SZ) or nrTMS targeting a control posterior parietal site (40HC and 40SZ). For the parietal site, the investigators will use the same TMS protocol parameters as the active nrTMS condition. Between and within group analyses will utilize repeated measures mixed-effects models to examine durability and generalizability of behavioral, cognitive, clinical and whole-brain neural oscillatory network changes (with focus on mPFC) after neuromodulation by active nrTMS at proximal, and distal post-nrTMS time-points, compared to control nrTMS of parietal site and baseline. Whole-brain correlations will be computed between neural activity (e.g., with focus on mPFC) related to self-agency during reality and speech monitoring tasks and behavior (e.g., self-generated retrieval accuracy and corrective response magnitude), and between neural activity with cognition, clinical symptoms and daily functioning).
- Conditions
- Schizophrenia
- Being tested
- TMS
- Keywords
- Schizophrenia, Transcranial Magnetic Stimulation, Prefrontal Cortex, Self-Agency, Reality Monitoring
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMSDevice
The investigators will use the NEXSTIM NAVIGATED BRAIN STIMULATION (NBS) SYSTEM to apply 10 Hz nrTMS to healthy controls (HC) and schizophrenia patients (SZ)
| Study group | Role | What they receive |
|---|---|---|
| Medial/Superior Prefrontal TMS | Active comparator | 10 Hz High frequency TMS applied to the mPFC Receives: Device: TMS |
| Posterior Parietal TMS | Placebo comparator | 10 Hz high frequency TMS applied to the posterior parietal cortex Receives: Device: TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
The PENN Cognitive battery is a validated assessment of cognition in which accuracy scores and reaction times will computed after TMS compared to baseline.The PENN Cognitive battery includes 10 brief cognitive tests, and the score ranges between 0 (worst possible performance) and 1000 (best possible performance).
Measured: 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)
Clinical Symptom Change will be measured by the validated SAPS and SANS over the past week after TMS compared to baseline. Possible scores depending on the sub scale can range from 0(Absent) to 7 (Extreme).
Measured: From baseline to immediate and distal time points after TMS, up to 4 weeks
Daily Functioning Change after TMS vs. Baseline (metrics of functioning)
Daily functioning will be measured with the Global Assessment of Functioning (GAF) scale over the past week, after TMS compared to baseline. Possible score range from 0 (inadequate information or in persistent danger of severely hurting self or others) to 100 (superior functioning in a wide range of activities)
Measured: From baseline to immediate and distal time points after TMS, up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2021
- Study start12 Nov 2020
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Karuna Subramaniam, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04807530
- Sponsor's protocol ID
- 122897
- Other IDs
- 1R01MH122897-01
- Acronym
- MESSI
- Status last verified
- Aug 2025
- First submitted
- 17 Mar 2021
- Last updated
- 29 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: De-identified data will include clinical, behavioral and cognitive scores, nrTMS data, and neuroimaging data. Neuroimaging data will include MEGI and structural MRI scans. All de-identified data will also be made available through presentations at scientific conferences, symposia, and seminars, as well as through publications in scientific journals. All University of California employees are committed to an open access policy to make all publications freely available. In compliance with this policy, all publications resulting from this proposal will be submitted for archiving on PubMed Central and BioRxiv.
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Causal Role of Medial Prefrontal Neural Activity in Self-Agency in Schizophrenia
- ClinicalTrials.gov ID
- NCT04807530
- Acronym / sponsor ID
- MESSI / 122897
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, Transcranial Magnetic Stimulation, Prefrontal Cortex, Self-Agency, Reality Monitoring
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 12 Nov 2020 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 19 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This longitudinal mechanistic randomized controlled trial in patients with schizophrenia (SZ) and matched healthy controls (HC) examines the underlying cause of self-agency deficits in SZ and their responsiveness to navigated repetitive transcranial magnetic stimulation (nrTMS) of the medial prefrontal cortex. Using a multimodal neuroimaging approach that combines structural MRI with functional magnetoencephalography imaging (MEGI) and nrTMS that is integrated with cognitive and clinical assessments, this research provides an unprecedented rigorous assessment of the neural and cognitive basis of self-agency and its modulation by nrTMS, using two distinct and validated paradigms involving speech monitoring (pitch perturbation) and reality monitoring.
Subjects will first be assessed for 1 week for diagnostic inclusion criteria and eligibility assessment. They will complete baseline assessments (i.e., cognitive, clinical and daily functioning assessments, structural MRI, and MEGI scans while they perform reality and speech monitoring tasks). After baseline assessments, 80 SZ and 80 age, gender, and education-matched HC will be randomly assigned to either active 10Hz nrTMS targeting mPFC (40HC and 40SZ) or nrTMS targeting a control posterior parietal site (40HC and 40SZ). For the parietal site, the investigators will use the same TMS protocol parameters as the active nrTMS condition. Between and within group analyses will utilize repeated measures mixed-effects models to examine durability and generalizability of behavioral, cognitive, clinical and whole-brain neural oscillatory network changes (with focus on mPFC) after neuromodulation by active nrTMS at proximal, and distal post-nrTMS time-points, compared to control nrTMS of parietal site and baseline. Whole-brain correlations will be computed between neural activity (e.g., with focus on mPFC) related to self-agency during reality and speech monitoring tasks and behavior (e.g., self-generated retrieval accuracy and corrective response magnitude), and between neural activity with cognition, clinical symptoms and daily functioning).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Medial/Superior Prefrontal TMS | Active comparator | Device: TMS10 Hz High frequency TMS applied to the mPFC |
| Posterior Parietal TMS | Placebo comparator | Device: TMS10 Hz high frequency TMS applied to the posterior parietal cortex |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Good general physical health
- English is first language
- No neurological disorder
- Meets MRI criteria
- No current alcohol or substance use disorder
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TMSThe investigators will use the NEXSTIM NAVIGATED BRAIN STIMULATION (NBS) SYSTEM to apply 10 Hz nrTMS to healthy controls (HC) and schizophrenia patients (SZ) | Device | Medial/Superior Prefrontal TMS, Posterior Parietal TMS |
Primary outcome
Self-Agency Behavioral Change during Reality Monitoring after TMS vs Baseline (metrics of accuracy)
Time frame: From baseline, to immediately after TMS, up to 1 week
Change in retrieval accuracy of self-generated information during reality monitoring task from baseline to post-TMS. No scales used.
Self-Agency Behavioral Change during Speech Monitoring after TMS vs Baseline (metrics of speech perturbation units)
Time frame: From baseline, to immediately after TMS, up to 1 week
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.
MEGI Neural Activity Change related to Self-Agency during Reality Monitoring after TMS vs Baseline (metrics of neural beta activation units)
Time frame: From baseline, to immediately after TMS, up to 1 week
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.
MEGI Neural Activity Change related to Self-Agency during Speech Monitoring after TMS vs Baseline (metrics of neural beta activation units)
Time frame: From baseline, to immediately after TMS, up to 1 week
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.
3 secondary outcomes
Cognition Change after TMS vs Baseline (metrics units of accuracy and speed of processing)
Time frame: 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)
Time frame: From baseline to immediate and distal time points after TMS, up to 4 weeks
Daily Functioning Change after TMS vs. Baseline (metrics of functioning)
Time frame: From baseline to immediate and distal time points after TMS, up to 4 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2025.
- Individual participant dataSharing planned: Yes. De-identified data will include clinical, behavioral and cognitive scores, nrTMS data, and neuroimaging data. Neuroimaging data will include MEGI and structural MRI scans. All de-identified data will also be made available through presentations at scientific conferences, symposia, and seminars, as well as through publications in scientific journals. All University of California employees are committed to an open access policy to make all publications freely available. In compliance with this policy, all publications resulting from this proposal will be submitted for archiving on PubMed Central and BioRxiv.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Miriam Mathew, PhD contact
Karuna Subramaniam, PhD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TMS in people with Schizophrenia, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Karuna Subramaniam, Ph.D (415-221-4810, karuna.subramaniam@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Self-Agency Behavioral Change during Reality Monitoring after TMS vs Baseline (metrics of accuracy) (time frame: From baseline, to immediately after TMS, up to 1 week). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2025.