- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04309370
Interactions of Fronto-Parietal High Frequency rTMS on Anterior Cingulate Cortex Activation in Schizophrenia (rTMS-FPCC)
Interactions of Fronto-Parietal High Frequency Repetitive Transcranial Magnetic Stimulation on Anterior Cingulate Cortex Activation in Schizophrenia
Study Overview
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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Megan M Gaunnac, MBA
- Phone Number: 3178808495
- Email: mmdelane@iupui.edu
Study Contact Backup
- Name: Andrew C Visco, MSW
- Phone Number: 3178808495
- Email: avisco@iupui.edu
Study Locations
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Indiana
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Indianapolis, Indiana, United States, 46202
- Prevention and Recovery Center for Early Psychosis
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Indianapolis, Indiana, United States, 46202
- IU Center for Neuroimaging
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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)
Exclusion Criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 20 Hz rTMS targeting the LDLPFC first, then 20 Hz rTMS targeting the LSPC
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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.
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Experimental: 20 Hz rTMS Targeting the LSPC first, then 20 Hz rTMS Targeting the LDLPFC
|
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in BOLD Signal in Anterior Cingulate Cortex
Time Frame: 1 day
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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.
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1 day
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Change in Cognitive Control Network Functional Connectivity
Time Frame: 1 day
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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.
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1 day
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Tom Hummer, PhD, Indiana University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1909015657
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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