SchizophreniarTMS-SRPNCT04068857
Repetitive Transcranial Magnetic Stimulation (rTMS) Self-Referential Processing (rTMS-SRP)
A study testing rTMS in people with Schizophrenia and Schizo Affective Disorder, run by Indiana University at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Schizophrenia, Schizo Affective Disorder
- What is being tested?
- rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2019to Dec 2020
- 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 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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:
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- 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).
Who cannot join
- 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
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- 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
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: Effects of Precuneus Repetitive Transcranial Magnetic Stimulation (rTMS) on Self-Referential Processing and Default Mode Network Functional Connectivity in Early Phase Psychosis
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.
Read the 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.
- Conditions
- Schizophrenia, Schizo Affective Disorder
- Being tested
- rTMS
- Keywords
- schizophrenia, schizoaffective disorder, psychosis, early phase
- 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.
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 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.
| Study group | Role | What they receive |
|---|---|---|
| rTMS | Experimental | Not described Receives: Device: rTMS |
| Sham | Sham comparator | Not described Receives: Device: rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
SRMP
To determine the effects of HF rTMS targeting the bilateral precuneus on SRP as measured by a self-referential memory paradigm (SRMP)
Measured: 1 week
Default mode network functional connectivity (DMN FC)
To assess the effects of HF rTMS targeting the bilateral precuneus on DMN FC at rest
Measured: 1 week
Secondary outcomes (4)
Correlation between SRMP and DMN FC
Assessing the correlation between SRMP performance and DMN FC
Measured: 1 week
SRMP and Scale to Assess Unawareness of Mental Disorder (SUM-D)
Assessing the correlation between SRMP performance and the SUM-D scale
Measured: 1 week
SRMP and Beck Cognitive Insight Scale (BCIS)
Assessing the correlation between SRMP performance and the BCIS scale
Measured: 1 week
SRMP and Birchwood Insight Scale
Assessing the correlation between SRMP performance and the Birchwood Insight Scale
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study startSep 2019 (estimated)
- Primary completionDec 2020 (estimated)
- Study completionDec 2020 (estimated)
Why it stopped: Study not going forward at this time.
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.
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Francis, Indiana University
- Investigators
- Michael Francis, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04068857
- Sponsor's protocol ID
- 1904511224
- Acronym
- rTMS-SRP
- Status last verified
- Nov 2019
- First submitted
- 21 Aug 2019
- Last updated
- 21 Nov 2019
- Results posted
- No
- 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 21 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Precuneus Repetitive Transcranial Magnetic Stimulation (rTMS) on Self-Referential Processing and Default Mode Network Functional Connectivity in Early Phase Psychosis
- ClinicalTrials.gov ID
- NCT04068857
- Acronym / sponsor ID
- rTMS-SRP / 1904511224
- Conditions
- Schizophrenia, Schizo Affective Disorder
- Keywords
- schizophrenia, schizoaffective disorder, psychosis, early phase
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study not going forward at this time.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- Sep 2019 (estimated)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 28 Aug 2019 (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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rTMS | Experimental | Device: rTMS |
| Sham | Sham comparator | Device: rTMS |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (15 listed)
- 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
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 |
|---|---|---|
| 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 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. | Device | Sham, rTMS |
Primary outcome
SRMP
Time frame: 1 week
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)
Time frame: 1 week
To assess the effects of HF rTMS targeting the bilateral precuneus on DMN FC at rest
4 secondary outcomes
Correlation between SRMP and DMN FC
Time frame: 1 week
SRMP and Scale to Assess Unawareness of Mental Disorder (SUM-D)
Time frame: 1 week
SRMP and Beck Cognitive Insight Scale (BCIS)
Time frame: 1 week
SRMP and Birchwood Insight Scale
Time frame: 1 week
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2019.
- 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.
Michael Francis, MD 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 rTMS in people with Schizophrenia and Schizo Affective Disorder, 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 9 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: withdrawn, as of the sponsor's last update on 21 Nov 2019. 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. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
SRMP (time frame: 1 week). 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 21 Nov 2019.