SchizophreniarTMS-FPCCNCT04309370
Interactions of Fronto-Parietal High Frequency rTMS on Anterior Cingulate Cortex Activation in Schizophrenia
A study testing 20 Hz rTMS in people with Schizophrenia, run by Indiana University at 2 sites in United States.
Trial summary
This will be a single site pilot study. 20 subjects with EPP (Early Phase Psychosis), defined as medical record documentation of the onset of clinically significant psychotic symptoms within the past 10 years, will be enrolled. Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- 20 Hz rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesUnited States
- Study dates
- 12 Mar 2020to 15 Apr 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Between 18 and 40 years of age
- Within 10 years of illness onset as defined by entry into treatment for psychotic symptoms
- Able to give informed consent
- Willing and able to adhere to the study schedule
- Mini-International Neuropsychiatric interview (MINI)37-40 diagnosis of schizophrenia
- Clinical stability defined by:
- Subjects must not have experienced an exacerbation of their illness within 4 weeks prior to randomization, leading to an intensification of psychiatric care in the opinion of the investigator. Examples of intensification of care include, but are not limited to: inpatient hospitalization, day/partial hospitalization, outpatient crisis management, or psychiatric treatment in an emergency room AND
- Antipsychotic treatment stability for at least 4 weeks prior to randomization (no change in antipsychotic dosing or addition of new antipsychotic medication)
Who cannot join
- Lifetime history of a seizure, excluding febrile seizures and those induced by substance withdrawal
- First degree relative with idiopathic epilepsy or other seizure disorder
- History of significant neurological illness
- History of head trauma as defined by a loss of consciousness or a post-concussive syndrome
- Pregnant or breast feeding
- Known IQ < 70 based on subject report
Show all 15Show fewer
- Current acute, serious, or unstable medical conditions
- Metallic objects planted in or near the head, including implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, ventriculoperitoneal shunt, or cochlear implants
- Contraindications to MRI or otherwise unable to tolerate MRI procedures
- History of electroconvulsive therapy
- Subjects taking clozapine
- Subjects who have participated in a clinical trial with any pharmacological treatment intervention for which they received study-related medication in the 4 weeks prior to randomization
- Subjects considered a high risk for suicidal acts - active suicidal ideation as determined by clinical interview OR any suicide attempt in 90 days prior to screening
- Current DSM-5 diagnosis of alcohol or drug use disorder (excluding nicotine or caffeine)
- Subjects who require concomitant treatment with prohibited medication, as specified in Attachment 2
Trial locations and contacts
2 sites in 1 country.
United States2 sites
IU Center for Neuroimaging
Indianapolis, Indiana, 46202
Prevention and Recovery Center for Early Psychosis
Indianapolis, Indiana, 46202
About this study
Official title: Interactions of Fronto-Parietal High Frequency Repetitive Transcranial Magnetic Stimulation on Anterior Cingulate Cortex Activation in Schizophrenia
This will be a single site pilot study. 20 subjects with EPP (Early Phase Psychosis), defined as medical record documentation of the onset of clinically significant psychotic symptoms within the past 10 years, will be enrolled. Prior to randomization subjects will undergo fMRI (Functional Magnetic Resonance Imaging) during CC (Cognitive Control) task (Stroop Color-Word paradigm) and resting-state paradigms. This baseline scan will also include a high-resolution structural sequence for neuronavigation purposes. Then, on two separate days, each occurring one-week apart, subjects will receive one session of excitatory (20 Hz) (Hertz) rTMS (Repetitive Transcranial Magnetic Stimulation) targeting the LDLPFC (Left Dorsolateral Prefrontal Cortex) and one session targeting the LSPC (Left Superior Parietal Cortex). The order of stimulation sites will be randomized and counter-balanced. Immediately following each session, subjects will undergo repeat fMRI during CC and RS (Resting State) paradigms. Investigators will also examine the effect of rTMS on CC performance.
Read the detailed description
In spite of existing work studying rTMS as a treatment modality in schizophrenia, there are no studies that have examined the effects of rTMS targeting superficial CCN (Cognitive Control Network) structures (LDLPFC and LSPC) on ACC (Anterior Cingulate Cortex) activity or CCN connectivity in schizophrenia. It is also important to note that the vast majority of studies using rTMS in schizophrenia have examined chronic populations where confounds associated with prolonged duration of illness may be present. EPP is a desirable population to study because these individuals tend to have fewer psychiatric and physical comorbidities and less antipsychotic drug exposure, all of which are factors that may confound investigations of new treatment interventions for this illness. In light of the significant unmet medical need associated with schizophrenia and the grave clinical effect of disrupted CC in the illness, rTMS modulating the ACC, and potentially CCN circuitry, represents an unexplored and novel potential treatment option.
The goal of this project is to utilize HF (20 Hz) rTMS, in conjunction with functional magnetic resonance imaging (fMRI), to provide evidence that rTMS targeting superficial CCN structures (LDLPFC and LSPC) modulates: 1) activation in the ACC during in-scanner CC task performance and 2) functional connectivity between the CCN structures during in-scanner CC task performance. This study will provide vital preliminary data on target engagement informing future clinical trials seeking to investigate rTMS as a novel treatment for CC impairment in schizophrenia. This study will also seek to refine the understanding of the brain circuitry that mediates the potential pro-CC effects of rTMS through the use of fMRI at baseline and following the course of rTMS administration.
- Conditions
- Schizophrenia
- Being tested
- 20 Hz rTMS
- Keywords
- schizophrenia, psychosis, early phase psychosis, rTMS
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
20 Hz rTMSDevice
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that received FDA clearance for use in treatment resistant major depressive disorder in 2008. rTMS utilizes the application of a repetitively pulsed magnetic field over the scalp to induce an electric field within a discrete area of the cerebral cortex. This electric field results in altered ion flow across the neuronal cellular membrane and ultimately changes in neuronal polarization. rTMS modulates cortical activation depending on the stimulation parameters used. Physiological studies have provided evidence that suggests that high-frequency (HF) rTMS produces an increase in local cortical excitability. Studies have also demonstrated that rTMS may increase or decrease functional connectivity between separate but related cortical structures, utilizing high and low frequency stimulation, respectively.
| Study group | Role | What they receive |
|---|---|---|
| 20 Hz rTMS targeting the LDLPFC first, then 20 Hz rTMS targeting the LSPC | Experimental | Not described Receives: Device: 20 Hz rTMS |
| 20 Hz rTMS Targeting the LSPC first, then 20 Hz rTMS Targeting the LDLPFC | Experimental | Not described Receives: Device: 20 Hz rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in BOLD Signal in Anterior Cingulate Cortex
Effects of rTMS on anterior cingulate cortex functional activation as measured by blood oxygen level dependent (BOLD) signal change scores during cognitive control Mismatch trials vs. Match trials (i.e., Mismatch - Match). The BOLD signal is measured during a functional magnetic resonance imaging (fMRI) scan and reflects the level of brain activity in the region. Change is calculated as difference between the Mismatch-Match signal at baseline and 30-60 minutes following the intervention. Higher scores indicate a larger increase in brain activity following the intervention.
Measured: 1 day
Change in Cognitive Control Network Functional Connectivity
The outcome reflects changes in blood oxygen level dependent (BOLD) functional connectivity with anterior cingulate cortex (ACC) and the left dorsolateral prefrontal cortex (LDLPFC) and left superior parietal cortex (LSPC). Functional connectivity is calculated as the Fisher's transformation of the correlation coefficient of the BOLD time series in the ACC with the time series in each target region. Therefore, functional connectivity reflects how similar brain activity is between the target regions (LDLPFC and LSPC) and the ACC, with higher scores indicating greater connectivity. Outcome scores are changes in this connectivity between baseline and 30-60 minutes following the rTMS intervention targeting LDLPFC or LSPC. Positive scores indicate stronger connectivity following rTMS in the cognitive control network.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2020
- Study start12 Mar 2020
- Primary completion15 Apr 2022
- Study completion15 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe 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
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tom Hummer, Indiana University
- Investigators
- Tom Hummer, PhD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04309370
- Sponsor's protocol ID
- 1909015657
- Acronym
- rTMS-FPCC
- Status last verified
- Jul 2023
- First submitted
- 20 Dec 2019
- Last updated
- 3 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interactions of Fronto-Parietal High Frequency Repetitive Transcranial Magnetic Stimulation on Anterior Cingulate Cortex Activation in Schizophrenia
- ClinicalTrials.gov ID
- NCT04309370
- Acronym / sponsor ID
- rTMS-FPCC / 1909015657
- Conditions
- Schizophrenia
- Keywords
- schizophrenia, psychosis, early phase psychosis, rTMS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- 12 Mar 2020 (actual)
- Primary completion
- 15 Apr 2022 (actual)
- Study completion
- 15 Apr 2022 (actual)
- First posted
- 16 Mar 2020 (actual)
- Results
- Posted 3 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be a single site pilot study. 20 subjects with EPP (Early Phase Psychosis), defined as medical record documentation of the onset of clinically significant psychotic symptoms within the past 10 years, will be enrolled. Prior to randomization subjects will undergo fMRI (Functional Magnetic Resonance Imaging) during CC (Cognitive Control) task (Stroop Color-Word paradigm) and resting-state paradigms. This baseline scan will also include a high-resolution structural sequence for neuronavigation purposes. Then, on two separate days, each occurring one-week apart, subjects will receive one session of excitatory (20 Hz) (Hertz) rTMS (Repetitive Transcranial Magnetic Stimulation) targeting the LDLPFC (Left Dorsolateral Prefrontal Cortex) and one session targeting the LSPC (Left Superior Parietal Cortex). The order of stimulation sites will be randomized and counter-balanced. Immediately following each session, subjects will undergo repeat fMRI during CC and RS (Resting State) paradigms. Investigators will also examine the effect of rTMS on CC performance.
Detailed description
In spite of existing work studying rTMS as a treatment modality in schizophrenia, there are no studies that have examined the effects of rTMS targeting superficial CCN (Cognitive Control Network) structures (LDLPFC and LSPC) on ACC (Anterior Cingulate Cortex) activity or CCN connectivity in schizophrenia. It is also important to note that the vast majority of studies using rTMS in schizophrenia have examined chronic populations where confounds associated with prolonged duration of illness may be present. EPP is a desirable population to study because these individuals tend to have fewer psychiatric and physical comorbidities and less antipsychotic drug exposure, all of which are factors that may confound investigations of new treatment interventions for this illness. In light of the significant unmet medical need associated with schizophrenia and the grave clinical effect of disrupted CC in the illness, rTMS modulating the ACC, and potentially CCN circuitry, represents an unexplored and novel potential treatment option.
The goal of this project is to utilize HF (20 Hz) rTMS, in conjunction with functional magnetic resonance imaging (fMRI), to provide evidence that rTMS targeting superficial CCN structures (LDLPFC and LSPC) modulates: 1) activation in the ACC during in-scanner CC task performance and 2) functional connectivity between the CCN structures during in-scanner CC task performance. This study will provide vital preliminary data on target engagement informing future clinical trials seeking to investigate rTMS as a novel treatment for CC impairment in schizophrenia. This study will also seek to refine the understanding of the brain circuitry that mediates the potential pro-CC effects of rTMS through the use of fMRI at baseline and following the course of rTMS administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 20 Hz rTMS targeting the LDLPFC first, then 20 Hz rTMS targeting the LSPC | Experimental | Device: 20 Hz rTMS |
| 20 Hz rTMS Targeting the LSPC first, then 20 Hz rTMS Targeting the LDLPFC | Experimental | Device: 20 Hz rTMS |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Between 18 and 40 years of age
- Within 10 years of illness onset as defined by entry into treatment for psychotic symptoms
- Able to give informed consent
- Willing and able to adhere to the study schedule
- Mini-International Neuropsychiatric interview (MINI)37-40 diagnosis of schizophrenia
Key exclusion criteria (15 listed)
- Lifetime history of a seizure, excluding febrile seizures and those induced by substance withdrawal
- First degree relative with idiopathic epilepsy or other seizure disorder
- History of significant neurological illness
- History of head trauma as defined by a loss of consciousness or a post-concussive syndrome
- Pregnant or breast feeding
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 |
|---|---|---|
| 20 Hz rTMSRepetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that received FDA clearance for use in treatment resistant major depressive disorder in 2008. rTMS utilizes the application of a repetitively pulsed magnetic field over the scalp to induce an electric field within a discrete area of the cerebral cortex. This electric field results in altered ion flow across the neuronal cellular membrane and ultimately changes in neuronal polarization. rTMS modulates cortical activation depending on the stimulation parameters used. Physiological studies have provided evidence that suggests that high-frequency (HF) rTMS produces an increase in local cortical excitability. Studies have also demonstrated that rTMS may increase or decrease functional connectivity between separate but related cortical structures, utilizing high and low frequency stimulation, respectively. | Device | 20 Hz rTMS Targeting the LSPC first, then 20 Hz rTMS Targeting the LDLPFC, 20 Hz rTMS targeting the LDLPFC first, then 20 Hz rTMS targeting the LSPC |
Primary outcome
Change in BOLD Signal in Anterior Cingulate Cortex
Time frame: 1 day
Effects of rTMS on anterior cingulate cortex functional activation as measured by blood oxygen level dependent (BOLD) signal change scores during cognitive control Mismatch trials vs. Match trials (i.e., Mismatch - Match). The BOLD signal is measured during a functional magnetic resonance imaging (fMRI) scan and reflects the level of brain activity in the region. Change is calculated as difference between the Mismatch-Match signal at baseline and 30-60 minutes following the intervention. Higher scores indicate a larger increase in brain activity following the intervention.
Change in Cognitive Control Network Functional Connectivity
Time frame: 1 day
The outcome reflects changes in blood oxygen level dependent (BOLD) functional connectivity with anterior cingulate cortex (ACC) and the left dorsolateral prefrontal cortex (LDLPFC) and left superior parietal cortex (LSPC). Functional connectivity is calculated as the Fisher's transformation of the correlation coefficient of the BOLD time series in the ACC with the time series in each target region. Therefore, functional connectivity reflects how similar brain activity is between the target regions (LDLPFC and LSPC) and the ACC, with higher scores indicating greater connectivity. Outcome scores are changes in this connectivity between baseline and 30-60 minutes following the rTMS intervention targeting LDLPFC or LSPC. Positive scores indicate stronger connectivity following rTMS in the cognitive control network.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Tom Hummer, PhD principal investigator
Indiana University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 20 Hz rTMS in people with Schizophrenia, run by Indiana University at 2 sites 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 8 inclusion and 15 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 3 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Yes. Results are posted in the registry (first posted 3 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in BOLD Signal in Anterior Cingulate Cortex (time frame: 1 day). The study lists 2 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 3 Aug 2023.