Repetitive Transcranial Magnetic Stimulation (rTMS) Self-Referential Processing (rTMS-SRP) (rTMS-SRP)
Primary Purpose
Schizophrenia, Schizo Affective Disorder
Status
Withdrawn
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
rTMS
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring schizophrenia, schizoaffective disorder, psychosis, early phase
Eligibility Criteria
Inclusion Criteria:
- Between 18 and 45 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
- Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (SCID-5) diagnosis of schizophrenia or schizoaffective disorder
Clinical stability as defined by:
- Clinical Global Impression scale - Severity (CGI-S) score of less than or equal to 4 (moderately ill) at baseline AND
- No 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 any new antipsychotic medication).
Exclusion Criteria:
- Lifetime history of a seizure, excluding febrile seizures and those induced by substance withdrawal
- First degree relative (that is, biological father, mother, brother, sister, or child) with idiopathic epilepsy or other seizure disorder
- History of significant neurological illness (including stroke, central nervous system (CNS) infection with persistent neurologic deficit, or other event deemed significant by PI)
- History of head trauma as defined by a loss of consciousness or a post-concussive syndrome
- Pregnant or breast feeding
- Known intelligence quotient (IQ) < 70 based on subject report
- Subjects with current acute, serious, or unstable medical conditions, including, but not limited to: inadequately controlled diabetes, asthma, chronic obstructive pulmonary disease (COPD), severe hypertriglyceridemia, recent cerebrovascular accidents, acute systemic infection or immunologic disease, unstable cardiovascular disorders, malnutrition, or hepatic, renal gastroenterological, respiratory, endocrine, neurologic, hematologic, or infectious diseases based on medical history or physical examination
- Metallic objects planted in or near the head, including implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, transcutaneous electrical nerve stimulation (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 SCID-5 diagnosis of substance use disorder (excluding nicotine or caffeine)
- Subjects who require concomitant treatment with prohibited medication, as specified in Attachment 2
Sites / Locations
- IU Center for Neuroimaging
- Prevention and Recovery Center for Early Psychosis
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
rTMS
Sham
Arm Description
Outcomes
Primary Outcome Measures
SRMP
To determine the effects of HF rTMS targeting the bilateral precuneus on SRP as measured by a self-referential memory paradigm (SRMP)
Default mode network functional connectivity (DMN FC)
To assess the effects of HF rTMS targeting the bilateral precuneus on DMN FC at rest
Secondary Outcome Measures
Correlation between SRMP and DMN FC
Assessing the correlation between SRMP performance and DMN FC
SRMP and Scale to Assess Unawareness of Mental Disorder (SUM-D)
Assessing the correlation between SRMP performance and the SUM-D scale
SRMP and Beck Cognitive Insight Scale (BCIS)
Assessing the correlation between SRMP performance and the BCIS scale
SRMP and Birchwood Insight Scale
Assessing the correlation between SRMP performance and the Birchwood Insight Scale
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04068857
Brief Title
Repetitive Transcranial Magnetic Stimulation (rTMS) Self-Referential Processing (rTMS-SRP)
Acronym
rTMS-SRP
Official Title
Effects of Precuneus Repetitive Transcranial Magnetic Stimulation (rTMS) on Self-Referential Processing and Default Mode Network Functional Connectivity in Early Phase Psychosis
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Withdrawn
Why Stopped
Study not going forward at this time.
Study Start Date
September 2019 (Anticipated)
Primary Completion Date
December 2020 (Anticipated)
Study Completion Date
December 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indiana University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This will be a single site pilot study. 16 subjects with early phase psychosis (EPP), defined as medical record documentation of the onset of clinically significant psychotic symptoms within the past ten years, will be randomized 1:1 to double-blind treatment with 5 sessions of rTMS or sham stimulation directed at the bilateral precuneus over the course of 1 week. Subjects will undergo functional magnetic resonance imaging (fMRI) procedures, behavioral and cognitive assessments, and self-referential memory paradigm (SRMP) at baseline and immediately following the final rTMS or sham session. Contact with subjects will be conducted at two weeks after the end of study intervention for adverse event assessments. In the event new adverse events felt to be related to the study intervention have occurred following the termination of study procedures, subjects will be brought in for further safety assessments.
Detailed Description
A number of studies have investigated the therapeutic potential of rTMS in schizophrenia, noting improvements in treatment refractory auditory hallucinations as well as negative symptoms and cognitive dysfunction. However, no previous studies have examined the effects of precuneus directed rTMS on SRP deficits 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. Early phase psychosis (EPP) is a desirable population to study because these patients 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 SRP in the illness, rTMS modulating precuneus, and potentially DMN circuitry, represents an unexplored and potentially novel potential treatment option.
This study proposes to examine the application of rTMS targeting the precuneus for the treatment of disrupted SRP in EPP. This is an important population for study because if effective, rTMS may represent a preventative treatment for the development of poor outcomes and functioning associated with SRP deficits in in schizophrenia. This study will also seek to refine the understanding of the brain circuitry that mediates the potential pro-SRP effects of rTMS through the use of fMRI at baseline and following the course of rTMS administration.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizo Affective Disorder
Keywords
schizophrenia, schizoaffective disorder, psychosis, early phase
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
rTMS
Arm Type
Experimental
Arm Title
Sham
Arm Type
Sham Comparator
Intervention Type
Device
Intervention Name(s)
rTMS
Intervention Description
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 and has become commonly used in clinical practice. 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 enables investigators to manipulate brain activity in a targeted cortical region as well as downstream connectivity within an associated neuronal circuit. High frequency (HF) rTMS leads to facilitatory effects on brain excitability. Previous studies have demonstrated that administration of as little as a single train or a small number of trains are able to produce an immediate increase in cortical excitability.
Primary Outcome Measure Information:
Title
SRMP
Description
To determine the effects of HF rTMS targeting the bilateral precuneus on SRP as measured by a self-referential memory paradigm (SRMP)
Time Frame
1 week
Title
Default mode network functional connectivity (DMN FC)
Description
To assess the effects of HF rTMS targeting the bilateral precuneus on DMN FC at rest
Time Frame
1 week
Secondary Outcome Measure Information:
Title
Correlation between SRMP and DMN FC
Description
Assessing the correlation between SRMP performance and DMN FC
Time Frame
1 week
Title
SRMP and Scale to Assess Unawareness of Mental Disorder (SUM-D)
Description
Assessing the correlation between SRMP performance and the SUM-D scale
Time Frame
1 week
Title
SRMP and Beck Cognitive Insight Scale (BCIS)
Description
Assessing the correlation between SRMP performance and the BCIS scale
Time Frame
1 week
Title
SRMP and Birchwood Insight Scale
Description
Assessing the correlation between SRMP performance and the Birchwood Insight Scale
Time Frame
1 week
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Between 18 and 45 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
Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (SCID-5) diagnosis of schizophrenia or schizoaffective disorder
Clinical stability as defined by:
Clinical Global Impression scale - Severity (CGI-S) score of less than or equal to 4 (moderately ill) at baseline AND
No 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 any new antipsychotic medication).
Exclusion Criteria:
Lifetime history of a seizure, excluding febrile seizures and those induced by substance withdrawal
First degree relative (that is, biological father, mother, brother, sister, or child) with idiopathic epilepsy or other seizure disorder
History of significant neurological illness (including stroke, central nervous system (CNS) infection with persistent neurologic deficit, or other event deemed significant by PI)
History of head trauma as defined by a loss of consciousness or a post-concussive syndrome
Pregnant or breast feeding
Known intelligence quotient (IQ) < 70 based on subject report
Subjects with current acute, serious, or unstable medical conditions, including, but not limited to: inadequately controlled diabetes, asthma, chronic obstructive pulmonary disease (COPD), severe hypertriglyceridemia, recent cerebrovascular accidents, acute systemic infection or immunologic disease, unstable cardiovascular disorders, malnutrition, or hepatic, renal gastroenterological, respiratory, endocrine, neurologic, hematologic, or infectious diseases based on medical history or physical examination
Metallic objects planted in or near the head, including implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, transcutaneous electrical nerve stimulation (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 SCID-5 diagnosis of substance use disorder (excluding nicotine or caffeine)
Subjects who require concomitant treatment with prohibited medication, as specified in Attachment 2
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Francis, MD
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
Facility Information:
Facility Name
IU Center for Neuroimaging
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Prevention and Recovery Center for Early Psychosis
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Repetitive Transcranial Magnetic Stimulation (rTMS) Self-Referential Processing (rTMS-SRP)
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