SchizophreniaNCT07155096
Accelerated DMN-Targeted cTBS to Modulate DMN Connectivity
A study testing Repetitive Transcranial Magnetic Stimulation in people with Schizophrenia, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
The central hypothesis is this: DMN connectivity can be modulated with inhibitory cTBS when delivered on an accelerated treatment schedule. This study seeks to provide evidence that accelerated, network-targeted inhibitory stimulation of the DMN leads to both altered network activity and a concomitant behavioral… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Repetitive Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Sep 2024to 5 Feb 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age between 18-65 years
- Diagnosis of either schizophrenia or schizoaffective disorder according to DSM-5 criteria and confirmed by SCID (First et al. 2015)
- Must be able to read, speak and understand English
- Must be judged by study staff to be capable of completing the study procedures
- Participants will be in stable outpatient psychiatric treatment and psychiatrically stable with no recent (within the past 30 days) psychiatric hospitalizations or changes in their psychiatric medication regimens.
Who cannot join
- • DSM-5 intellectual disability
- Substance use disorder (other than nicotine) within the past three months
- Current, active suicidal ideation with intent or plan, as assessed by a score of 5 or higher on the Brief Psychiatric Rating Scale question #4 Suicidality.
- Positive urine drug screen for illicit substance use that can increase seizure risk (cocaine, benzodiazepines, amphetamine, methamphetamine)
- Any history of a progressive or genetic neurologic disorder (e.g. Parkinson's disease, multiple sclerosis, tuberous sclerosis, Alzheimer's Disease) or acquired neurological disease (e.g. stroke, traumatic brain injury, tumor), including intracranial lesions
- History of head trauma resulting in any loss of consciousness (>15 minutes) or neurological sequelae
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- Current history of poorly controlled headaches including chronic medication for migraine prevention
- History of fainting spells of unknown or undetermined etiology that might constitute seizures
- History of seizures, diagnosis of epilepsy, or immediate (1st degree relative) family history epilepsy with the exception of a single seizure of benign etiology (e.g. febrile seizures) in the judgment of a board-certified neurologist
- Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.)
- Any metal in the brain or skull (excluding dental fillings) or elsewhere in the body unless cleared by the responsible covering MD (e.g. MRI compatible joint replacement)
- Any devices such as pacemaker, medication pump, nerve stimulator, TENS unit, ventriculo-peritoneal shunt unless cleared by the responsible covering MD
- All female participants of child-bearing age will be required to have a pregnancy test; any participant who is pregnant or planning to become pregnant will not be enrolled in the study
- Medications will be reviewed by the responsible covering physician and a decision about inclusion will be made based on the participant's past medical history, drug dose, history of recent medication changes or duration of treatment, and use of CNS active drugs. The published TMS guidelines review of medications to be considered with rTMS will be taken into consideration given their described effects on cortical excitability measures.
- Any changes in medications or hospitalizations within the past 30 days.
- Participants who, in the investigator's opinion, might not be suitable for the study or would be unable to tolerate the study visit
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt Psychiatric Hospital
Nashville, Tennessee, 37212
About this study
The central hypothesis is this: DMN connectivity can be modulated with inhibitory cTBS when delivered on an accelerated treatment schedule. This study seeks to provide evidence that accelerated, network-targeted inhibitory stimulation of the DMN leads to both altered network activity and a concomitant behavioral change in cognitive performance in individuals with schizophrenia and schizoaffective disorder. This study will also compare the effect of inhibitory cTBS in healthy individuals, as it may also lead to both altered network activity and a behavioral change in cognitive performance in individuals without schizophrenia or schizoaffective disorder.
If successful, this study will have identified a safe, effective, and broadly applicable treatment for cognitive impairment in schizophrenia that has potential for translation into many other psychiatric and neurodevelopmental disorders, such as autism.
Read the detailed description
Schizophrenia and other psychotic disorders are disabling, lifelong illnesses that afflict over three million people in the US. Schizophrenia is characterized by positive symptoms (i.e., delusions, hallucinations), negative symptoms (i.e., anhedonia, amotivation), and cognitive impairment. Cognitive impairment is a devastating, central and enduring feature of schizophrenia that is a leading cause of disability. Nearly 94% of people with schizophrenia have at least one cognitive symptom. However, there are no current treatments for cognitive impairment in schizophrenia.
DMN hyperconnectivity has been observed across multiple psychiatric disorders, including schizophrenia. DMN disruption in schizophrenia is a well-replicated observation. DMN disorganization has been consistently observed in individuals with schizophrenia and their first-degree relatives and has been associated with cognitive impairment, positive symptoms, negative symptoms, and nicotine use. Therefore, DMN connectivity may be a potential biomarker and treatment target for cognitive impairment across multiple psychiatric disorders, including schizophrenia and autism.
Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive brain stimulation that uses electromagnetic fields to change neuronal patterns of connectivity in brain networks. When international safety guidelines are followed, rTMS is a safe and well-tolerated intervention in individuals with and without psychiatric illness (Rossi et al. 2021). rTMS is also a versatile research tool whose stimulation parameters can be changed. Depending on the parameters, rTMS can be excitatory or inhibitory and can increase or decrease network connectivity. Specifically, intermittent theta burst stimulation (iTBS) is excitatory, while continuous theta burst stimulation (cTBS) is inhibitory. In this protocol, inhibitory cTBS is used to reduce DMN connectivity and improve cognitive performance. rTMS has been successfully used to modulate DMN connectivity in healthy individuals and in individuals with psychosis. rTMS is FDA-approved for the treatment of major depressive disorder, obsessive-compulsive disorder, and smoking cessation.
Previous studies by our group and others have demonstrated the ability of rTMS to change patterns of activity in cortical networks of the human brain. In addition, researchers have also previously demonstrated the ability to both increase and decrease connectivity within a specific network (e.g. DMN) by neuroanatomically targeted rTMS. In the present study, an accelerated inhibitory cTBS intervention will be delivered to the left parietal node of the DMN, a network key to attentional performance. The PI has conducted clinical trials testing both single and multiple sessions of cTBS to the parietal node of the DMN. cTBS applied to the parietal cortex has been well tolerated, and there have been no serious adverse events, including no worsening of psychosis or depression, and no seizures. In fact, 5 sessions of DMN-targeted cTBS (which will be used in this study) significantly reduced nicotine craving in schizophrenia. cTBS has also been investigated as a treatment for seizures.
In most clinical and research protocols, rTMS is traditionally applied in daily sessions for 4-6 weeks. However, accelerated protocols have recently consolidated treatment into multiple rTMS sessions per day, thereby reducing treatment duration and shortening time to achieve clinical response. Accelerated protocols also offer significant advantages for other clinical populations, such as neurodevelopmental disorders, where daily treatment over multiple weeks may not be feasible. Currently, an FDA-cleared accelerated rTMS for depression involves treatment with 10 excitatory rTMS sessions/day for 5 days (i.e., 50 rTMS sessions over 1 week). In the current protocol, this study will test 5 inhibitory cTBS sessions delivered in 1 day.
Our central hypothesis is this: DMN connectivity can be modulated with inhibitory cTBS when delivered on an accelerated treatment schedule. This study seeks to provide evidence that accelerated, network-targeted inhibitory stimulation of the DMN leads to both altered network activity and a concomitant behavioral change in cognitive performance in individuals with schizophrenia and schizoaffective disorder. This study will also compare the effect of inhibitory cTBS in healthy individuals, as it may also lead to both altered network activity and a behavioral change in cognitive performance in individuals without schizophrenia or schizoaffective disorder.
If successful, this study will have identified a safe, effective, and broadly applicable treatment for cognitive impairment in schizophrenia that has potential for translation into many other psychiatric and neurodevelopmental disorders, such as autism.
- Conditions
- Schizophrenia
- Being tested
- Repetitive Transcranial Magnetic Stimulation
- Keywords
- schizophrenia, rTMS, TMS, fMRI, DMN
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive Transcranial Magnetic StimulationDevice
Repetitive Transcranial Magnetic Stimulation (rTMS): Participants will each receive Default Mode Network-targeted continuous theta burst stimulation (cTBS) administered at 100% Active Motor Threshold
| Study group | Role | What they receive |
|---|---|---|
| Default Mode Network-Targeted cTBS | Experimental | All participants receive 5 sessions of active cTBS (600 pulses) to the DMN, with a 30-minute inter-session interval. Receives: Device: Repetitive Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional Connectivity Changes
We will determine if an accelerated inhibitory cTBS protocol targeted to the DMN is associated with a decrease in functional connectivity before and after cTBS
Measured: From enrollment to the end of MRI, maximum 3 weeks.
Secondary outcomes (1)
Cognitive Performance
As an exploratory analysis, we will also determine if change in DMN functional connectivity is associated with change in cognitive performance.
Measured: From enrollment to the end of the study, maximum 3 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2025
- Study start9 Sep 2024
- Primary completion29 Jan 2026
- Study completion5 Feb 2026
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 Vanderbilt University Medical CenterThe 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
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Heather Burrell Ward, Vanderbilt University Medical Center
- Investigators
- Heather Ward, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07155096
- Sponsor's protocol ID
- 232140
- Status last verified
- Sep 2026
- First submitted
- 26 Aug 2025
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: This study is not NIH-funded, so public data sharing is not required. Reasonable requests for data sharing will be considered.
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Accelerated DMN-Targeted cTBS to Modulate DMN Connectivity
- ClinicalTrials.gov ID
- NCT07155096
- Acronym / sponsor ID
- 232140
- Conditions
- Schizophrenia
- Keywords
- schizophrenia, rTMS, TMS, fMRI, DMN
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- 9 Sep 2024 (actual)
- Primary completion
- 29 Jan 2026 (actual)
- Study completion
- 5 Feb 2026 (actual)
- First posted
- 4 Sep 2025 (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.
The central hypothesis is this: DMN connectivity can be modulated with inhibitory cTBS when delivered on an accelerated treatment schedule. This study seeks to provide evidence that accelerated, network-targeted inhibitory stimulation of the DMN leads to both altered network activity and a concomitant behavioral change in cognitive performance in individuals with schizophrenia and schizoaffective disorder. This study will also compare the effect of inhibitory cTBS in healthy individuals, as it may also lead to both altered network activity and a behavioral change in cognitive performance in individuals without schizophrenia or schizoaffective disorder.
If successful, this study will have identified a safe, effective, and broadly applicable treatment for cognitive impairment in schizophrenia that has potential for translation into many other psychiatric and neurodevelopmental disorders, such as autism.
Detailed description
Schizophrenia and other psychotic disorders are disabling, lifelong illnesses that afflict over three million people in the US. Schizophrenia is characterized by positive symptoms (i.e., delusions, hallucinations), negative symptoms (i.e., anhedonia, amotivation), and cognitive impairment. Cognitive impairment is a devastating, central and enduring feature of schizophrenia that is a leading cause of disability. Nearly 94% of people with schizophrenia have at least one cognitive symptom. However, there are no current treatments for cognitive impairment in schizophrenia.
DMN hyperconnectivity has been observed across multiple psychiatric disorders, including schizophrenia. DMN disruption in schizophrenia is a well-replicated observation. DMN disorganization has been consistently observed in individuals with schizophrenia and their first-degree relatives and has been associated with cognitive impairment, positive symptoms, negative symptoms, and nicotine use. Therefore, DMN connectivity may be a potential biomarker and treatment target for cognitive impairment across multiple psychiatric disorders, including schizophrenia and autism.
Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive brain stimulation that uses electromagnetic fields to change neuronal patterns of connectivity in brain networks. When international safety guidelines are followed, rTMS is a safe and well-tolerated intervention in individuals with and without psychiatric illness (Rossi et al. 2021). rTMS is also a versatile research tool whose stimulation parameters can be changed. Depending on the parameters, rTMS can be excitatory or inhibitory and can increase or decrease network connectivity. Specifically, intermittent theta burst stimulation (iTBS) is excitatory, while continuous theta burst stimulation (cTBS) is inhibitory. In this protocol, inhibitory cTBS is used to reduce DMN connectivity and improve cognitive performance. rTMS has been successfully used to modulate DMN connectivity in healthy individuals and in individuals with psychosis. rTMS is FDA-approved for the treatment of major depressive disorder, obsessive-compulsive disorder, and smoking cessation.
Previous studies by our group and others have demonstrated the ability of rTMS to change patterns of activity in cortical networks of the human brain. In addition, researchers have also previously demonstrated the ability to both increase and decrease connectivity within a specific network (e.g. DMN) by neuroanatomically targeted rTMS. In the present study, an accelerated inhibitory cTBS intervention will be delivered to the left parietal node of the DMN, a network key to attentional performance. The PI has conducted clinical trials testing both single and multiple sessions of cTBS to the parietal node of the DMN. cTBS applied to the parietal cortex has been well tolerated, and there have been no serious adverse events, including no worsening of psychosis or depression, and no seizures. In fact, 5 sessions of DMN-targeted cTBS (which will be used in this study) significantly reduced nicotine craving in schizophrenia. cTBS has also been investigated as a treatment for seizures.
In most clinical and research protocols, rTMS is traditionally applied in daily sessions for 4-6 weeks. However, accelerated protocols have recently consolidated treatment into multiple rTMS sessions per day, thereby reducing treatment duration and shortening time to achieve clinical response. Accelerated protocols also offer significant advantages for other clinical populations, such as neurodevelopmental disorders, where daily treatment over multiple weeks may not be feasible. Currently, an FDA-cleared accelerated rTMS for depression involves treatment with 10 excitatory rTMS sessions/day for 5 days (i.e., 50 rTMS sessions over 1 week). In the current protocol, this study will test 5 inhibitory cTBS sessions delivered in 1 day.
Our central hypothesis is this: DMN connectivity can be modulated with inhibitory cTBS when delivered on an accelerated treatment schedule. This study seeks to provide evidence that accelerated, network-targeted inhibitory stimulation of the DMN leads to both altered network activity and a concomitant behavioral change in cognitive performance in individuals with schizophrenia and schizoaffective disorder. This study will also compare the effect of inhibitory cTBS in healthy individuals, as it may also lead to both altered network activity and a behavioral change in cognitive performance in individuals without schizophrenia or schizoaffective disorder.
If successful, this study will have identified a safe, effective, and broadly applicable treatment for cognitive impairment in schizophrenia that has potential for translation into many other psychiatric and neurodevelopmental disorders, such as autism.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Default Mode Network-Targeted cTBS | Experimental | Device: Repetitive Transcranial Magnetic StimulationAll participants receive 5 sessions of active cTBS (600 pulses) to the DMN, with a 30-minute inter-session interval. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age between 18-65 years
- Diagnosis of either schizophrenia or schizoaffective disorder according to DSM-5 criteria and confirmed by SCID (First et al. 2015)
- Must be able to read, speak and understand English
- Must be judged by study staff to be capable of completing the study procedures
- Participants will be in stable outpatient psychiatric treatment and psychiatrically stable with no recent (within the past 30 days) psychiatric hospitalizations or changes in their psychiatric medication regimens.
Key exclusion criteria (16 listed)
- • DSM-5 intellectual disability
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 |
|---|---|---|
| Repetitive Transcranial Magnetic StimulationRepetitive Transcranial Magnetic Stimulation (rTMS): Participants will each receive Default Mode Network-targeted continuous theta burst stimulation (cTBS) administered at 100% Active Motor Threshold | Device | Default Mode Network-Targeted cTBS |
Primary outcome
Functional Connectivity Changes
Time frame: From enrollment to the end of MRI, maximum 3 weeks.
We will determine if an accelerated inhibitory cTBS protocol targeted to the DMN is associated with a decrease in functional connectivity before and after cTBS
1 secondary outcome
Cognitive Performance
Time frame: From enrollment to the end of the study, maximum 3 weeks.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Individual participant dataSharing planned: No. This study is not NIH-funded, so public data sharing is not required. Reasonable requests for data sharing will be considered.
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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. This study is not recruiting at the moment.
Heather Ward, MD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repetitive Transcranial Magnetic Stimulation in people with Schizophrenia, run by Vanderbilt University Medical Center 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 5 inclusion and 16 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: finished, as of the sponsor's last update on 15 Sep 2026. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional Connectivity Changes (time frame: From enrollment to the end of MRI, maximum 3 weeks.). 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 15 Sep 2026.