SchizophreniaEmeraldThunderNCT02131129
rTMS in First Episode Psychosis
A study testing rTMS in people with Schizophrenia and Schizophreniform Disorder, run by Indiana University at 2 sites in United States.
Trial summary
This study proposes to examine the application of rTMS for the treatment of cognitive dysfunction in FEP. This is an important population for study because if effective, rTMS may represent a preventative treatment for the development of social and vocational impairment that is associated with cognitive dysfunction in… Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Schizophrenia, Schizophreniform Disorder, Schizoaffective 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
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- 30 Apr 2014to Dec 2016
- 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
- 18-40 years of age at study entry
- Male or female
- DSM IV-TR Diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder as confirmed by Structured Clinical Interview for DSM-IV-TR (SCID)44
- Subjects in their first-episode of psychosis, defined as the onset of clinically significant psychotic symptoms within the past five years as determined by first medical record documentation of these conditions
- BACS composite t-score of 40 or less at baseline assessment
- Clinical stability as defined by:
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- CGI-S score of less than or equal to 4 (moderately ill) at randomization AND
- 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 any new antipsychotic medication).
- Able to give informed consent
- Subjects must be willing and able to adhere to study schedule
- Outpatient or Inpatient treatment status
- Female subjects of childbearing potential must test negative for pregnancy at screening and baseline visit
Who cannot join
- Life-time history of a seizure, excluding febrile seizures and those induced by substance withdrawal
- 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
- 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, 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 deemed significant by PI
- Pregnancy or breast feeding
Show all 14Show fewer
- Known IQ < 70 based on medical history
- Current DSM-IV-TR diagnosis of alcohol or drug dependence (excluding nicotine or caffeine)
- Subjects with current acute, serious, or unstable medical conditions, including, but not limited to: inadequately controlled diabetes, asthma, 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.
- Subjects with contraindications to MRI or otherwise unable to tolerate MRI procedure
- 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
- 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 who require concomitant treatment with prohibited medication, as specified in Attachment 2
- Subjects with a history of electroconvulsive therapy
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: Cortical Activation and Cognitive Performance During Repetitive Transcranial Magnetic Stimulation in First-Episode Psychosis: A Pilot Study
This study proposes to examine the application of rTMS for the treatment of cognitive dysfunction in FEP. This is an important population for study because if effective, rTMS may represent a preventative treatment for the development of social and vocational impairment that is associated with cognitive dysfunction in schizophrenia. This study will also seek to refine the understanding of the brain circuitry that mediates the potential pro-cognitive effects of rTMS through the use of functional magnetic resonance imaging (fMRI) at baseline and following the course of rTMS administration.
Read the detailed description
Schizophrenia is a chronic and disabling illness that typically begins in the late teen and early adult years.1 This illness is associated with significant impairments in areas such as independent living, social functioning, and vocational functioning.2 Indeed, only 10% of people with schizophrenia are employed, translating into annual lost wages of nearly 15 billion dollars.3,4 Schizophrenia also represents an important societal burden as this illness has been estimated to cost over 40 billion dollars each year in the United States alone.5
Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment for neuropsychiatric illness. A non-invasive intervention, 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. The end result is altered neuronal activity in the area of the cerebral cortex where the rTMS is applied.12 rTMS is a safe and well-tolerated intervention that received FDA approval for treatment refractory major depressive disorder in 2008 and has since become commonly used in clinical practice.13
This study proposes to examine the application of rTMS for the treatment of cognitive dysfunction in FEP. This is an important population for study because if effective, rTMS may represent a preventative treatment for the development of social and vocational impairment that is associated with cognitive dysfunction in schizophrenia. This study will also seek to refine the understanding of the brain circuitry that mediates the potential pro-cognitive effects of rTMS through the use of functional magnetic resonance imaging (fMRI) at baseline and following the course of rTMS administration.
- Being tested
- rTMS, Sham Comparator
- Keywords
- schizophrenia, schizophreniform disorder, schizoaffective disorder, first episode, psychosis, cognition
- 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
Also called NeuroStar
The stimulation sites will be the left and right DLPFC, defined as 5 cm anterior to the scalp positions at which the MTs were determined. Treatments will be delivered within the following stimulation parameters: 110% of MT, 20 Hz, 30 trains, 1.0 second per train, 20 pulses per train, inter-train interval of 30 seconds (600 pulses/hemisphere, for a total of 1200 pulses/session/day).
Ten sessions over a two week duration
Sham ComparatorDevice
Also called NeuroStar
The stimulation sites will be the left and right DLPFC, defined as 5 cm anterior to the scalp positions at which the MTs were determined. Treatments will be delivered within the following stimulation parameters: 110% of MT, 20 Hz, 30 trains, 1.0 second per train, 20 pulses per train, inter-train interval of 30 seconds (600 pulses/hemisphere, for a total of 1200 pulses/session/day).
Ten sessions over a two week duration
| Study group | Role | What they receive |
|---|---|---|
| rTMS | Experimental | The stimulation sites will be the left and right DLPFC, defined as 5 cm anterior to the scalp positions at which the MTs were determined. Treatments will be delivered within the following stimulation parameters: 110% of MT, 20 Hz, 30 trains, 1.0 second per train, 20 pulses per train, inter-train interval of 30 seconds (600 pulses/hemisphere, for a total of 1200 pulses/session/day). Receives: Device: rTMS |
| Sham | Sham comparator | The stimulation sites will be the left and right DLPFC, defined as 5 cm anterior to the scalp positions at which the MTs were determined. Treatments will be delivered within the following stimulation parameters: 110% of MT, 20 Hz, 30 trains, 1.0 second per train, 20 pulses per train, inter-train interval of 30 seconds (600 pulses/hemisphere, for a total of 1200 pulses/session/day). Receives: Device: Sham Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive Performance
rTMS effectiveness in improving cognitive performance as measured by the Brief Assessment of Cognition in Schizophrenia (BACS) composite score. The BACS is a battery specifically designed to measure treatment-related changes in cognition, and has alternate forms, thus minimizing practice effects. The battery includes brief assessments of executive functions, verbal fluency, attention, verbal memory, working memory and motor speed, and generates a composite score that is calculated by summing t-scores derived by comparisons with a normative sample of 404 healthy controls. The six brief assessments' t-scores, are summed, and averaged to provide a composite t-score. The composite score min and max are between -43 and 100. A higher score indicating better cognitive performance. The composite score is reported as a change score relative to baseline for both.
Measured: For within-group comparisons, scores at V13 (day 15) and V14 (follow-up two weeks after V13) were compared to baseline
Cortical Activation
effects of rTMS on cortical activation using fMRI during working memory and episodic memory tasks
Measured: Change from Baseline (day 1) to Visit 13 (day 15)
Secondary outcomes (4)
Cognitive Performance
rTMS effectiveness in improving cognitive performance was assessed by the Trail Making Test-Part B change score and performance on the Trail Making Test-Part B. The Trail Making Test-Part B is a measure of visual attention and task switching. The task requires a subject to 'connect-the-dots' of 25 consecutive targets on a sheet of paper. In Part B version the subject alternates between numbers and letters (1, A, 2, B, etc.) The goal of the test is for the subject is to finish part B as quickly as possible, the time taken to complete the test is used as the primary performance metric.
Measured: 14 days
Cognitive Performance
rTMS effectiveness in improving cognitive performance as measured by the Brief Assessment of Cognition in Schizophrenia (BACS) composite score. The BACS is a battery specifically designed to measure treatment-related changes in cognition by utilizing 6 tasks, and has alternate forms, thus minimizing practice effects. Each task generates a raw score (with a higher score indicating better performance): verbal memory 0-75; digit sequencing 0-28; token motor task 0-100; semantic\&letter fluency 0-148; symbol coding 0-110; and tower of London 0-22. The raw scores are used to generate a composite score that is calculated by summing t-scores derived by comparisons with a normative sample of 404 healthy controls. The six brief assessments' t-scores, are summed, and averaged to provide a composite t-score. The composite score min and max are between -43 and 100. A higher score indicating better cognitive performance.
Measured: 14 days
Symptoms
rTMS effectiveness in general symptomatology assessed by the Positive and Negative Syndrome Scale (PANSS). The PANSS is a semi-structured interview, containing 30 items that assess symptoms of psychotic disorders including positive, negative, and general psychopathology symptoms. Positive symptoms are rated on 7 items, negative symptoms are rated on 7 items, and general psychopathology on 16 items. Scores for each item range from 1=absent to 7=extreme. Positive, negative, and general psychopathology symptoms can each respectively render total scores. Positive total scores ranging from 7-49, negative total scores ranging from 7-49, and general psychopathology scores ranging from 16-112. When all items are summed together a total score is generated. Total scores for all items range from 30-210, a lower score reflecting fewer symptoms.
Measured: For within-group comparisons, scores at V13 (day 15) and V14 (follow-up two weeks after V13) were compared to baseline
Negative Symptoms
rTMS effectiveness in reducing negative symptoms as measured by the negative symptom assessment scale (NSA-16). The NSA-16 is used to help clinicians rate behaviors (not psychopathology) commonly associated with negative symptoms of schizophrenia. The scale rates subjects on 16 "anchors," is a semi-structured, clinical interview, and each item is rated from 1 to 6. The total score is the sum of the 16 specific items and ranges from 16 to 96; a higher score indicates greater severity of illness. In addition, there is a global rating that represents the overall assessment of a subject's negative symptoms. The rating should not be an average of any particular behavior, but a gestalt of everything observed in the interview.
Measured: Assessed at Baseline (day 0), Midpoint (day 8), and Endpoint (day 15)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2014 (estimated)
- Study start30 Apr 2014
- Primary completionDec 2016
- Study completionDec 2016
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.
- 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- Neuronetics
- Responsible party
- Principal investigator, Michael Francis, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02131129
- Sponsor's protocol ID
- 1401416429
- Acronym
- EmeraldThunder
- Status last verified
- Mar 2023
- First submitted
- 2 May 2014
- Last updated
- 19 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cortical Activation and Cognitive Performance During Repetitive Transcranial Magnetic Stimulation in First-Episode Psychosis: A Pilot Study
- ClinicalTrials.gov ID
- NCT02131129
- Acronym / sponsor ID
- EmeraldThunder / 1401416429
- Keywords
- schizophrenia, schizophreniform disorder, schizoaffective disorder, first episode, psychosis, cognition
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- Neuronetics
- Study start
- 30 Apr 2014 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 6 May 2014 (estimated)
- Results
- Posted 29 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study proposes to examine the application of rTMS for the treatment of cognitive dysfunction in FEP. This is an important population for study because if effective, rTMS may represent a preventative treatment for the development of social and vocational impairment that is associated with cognitive dysfunction in schizophrenia. This study will also seek to refine the understanding of the brain circuitry that mediates the potential pro-cognitive effects of rTMS through the use of functional magnetic resonance imaging (fMRI) at baseline and following the course of rTMS administration.
Detailed description
Schizophrenia is a chronic and disabling illness that typically begins in the late teen and early adult years.1 This illness is associated with significant impairments in areas such as independent living, social functioning, and vocational functioning.2 Indeed, only 10% of people with schizophrenia are employed, translating into annual lost wages of nearly 15 billion dollars.3,4 Schizophrenia also represents an important societal burden as this illness has been estimated to cost over 40 billion dollars each year in the United States alone.5
Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment for neuropsychiatric illness. A non-invasive intervention, 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. The end result is altered neuronal activity in the area of the cerebral cortex where the rTMS is applied.12 rTMS is a safe and well-tolerated intervention that received FDA approval for treatment refractory major depressive disorder in 2008 and has since become commonly used in clinical practice.13
This study proposes to examine the application of rTMS for the treatment of cognitive dysfunction in FEP. This is an important population for study because if effective, rTMS may represent a preventative treatment for the development of social and vocational impairment that is associated with cognitive dysfunction in schizophrenia. This study will also seek to refine the understanding of the brain circuitry that mediates the potential pro-cognitive effects of rTMS through the use of functional magnetic resonance imaging (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: rTMSThe stimulation sites will be the left and right DLPFC, defined as 5 cm anterior to the scalp positions at which the MTs were determined. Treatments will be delivered within the following stimulation parameters: 110% of MT, 20 Hz, 30 trains, 1.0 second per train, 20 pulses per train, inter-train interval of 30 seconds (600 pulses/hemisphere, for a total of 1200 pulses/session/day). |
| Sham | Sham comparator | Device: Sham ComparatorThe stimulation sites will be the left and right DLPFC, defined as 5 cm anterior to the scalp positions at which the MTs were determined. Treatments will be delivered within the following stimulation parameters: 110% of MT, 20 Hz, 30 trains, 1.0 second per train, 20 pulses per train, inter-train interval of 30 seconds (600 pulses/hemisphere, for a total of 1200 pulses/session/day). |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- 18-40 years of age at study entry
- Male or female
- DSM IV-TR Diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder as confirmed by Structured Clinical Interview for DSM-IV-TR (SCID)44
- Subjects in their first-episode of psychosis, defined as the onset of clinically significant psychotic symptoms within the past five years as determined by first medical record documentation of these conditions
- BACS composite t-score of 40 or less at baseline assessment
Key exclusion criteria (14 listed)
- Life-time history of a seizure, excluding febrile seizures and those induced by substance withdrawal
- 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
- 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, 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 deemed significant by PI
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 |
|---|---|---|
| rTMSAlso: NeuroStarThe stimulation sites will be the left and right DLPFC, defined as 5 cm anterior to the scalp positions at which the MTs were determined. Treatments will be delivered within the following stimulation parameters: 110% of MT, 20 Hz, 30 trains, 1.0 second per train, 20 pulses per train, inter-train interval of 30 seconds (600 pulses/hemisphere, for a total of 1200 pulses/session/day). Ten sessions over a two week duration | Device | rTMS |
| Sham ComparatorAlso: NeuroStarThe stimulation sites will be the left and right DLPFC, defined as 5 cm anterior to the scalp positions at which the MTs were determined. Treatments will be delivered within the following stimulation parameters: 110% of MT, 20 Hz, 30 trains, 1.0 second per train, 20 pulses per train, inter-train interval of 30 seconds (600 pulses/hemisphere, for a total of 1200 pulses/session/day). Ten sessions over a two week duration | Device | Sham |
Primary outcome
Cognitive Performance
Time frame: For within-group comparisons, scores at V13 (day 15) and V14 (follow-up two weeks after V13) were compared to baseline
rTMS effectiveness in improving cognitive performance as measured by the Brief Assessment of Cognition in Schizophrenia (BACS) composite score. The BACS is a battery specifically designed to measure treatment-related changes in cognition, and has alternate forms, thus minimizing practice effects. The battery includes brief assessments of executive functions, verbal fluency, attention, verbal memory, working memory and motor speed, and generates a composite score that is calculated by summing t-scores derived by comparisons with a normative sample of 404 healthy controls. The six brief assessments' t-scores, are summed, and averaged to provide a composite t-score. The composite score min and max are between -43 and 100. A higher score indicating better cognitive performance. The composite score is reported as a change score relative to baseline for both.
Cortical Activation
Time frame: Change from Baseline (day 1) to Visit 13 (day 15)
effects of rTMS on cortical activation using fMRI during working memory and episodic memory tasks
4 secondary outcomes
Cognitive Performance
Time frame: 14 days
Cognitive Performance
Time frame: 14 days
Symptoms
Time frame: For within-group comparisons, scores at V13 (day 15) and V14 (follow-up two weeks after V13) were compared to baseline
Negative Symptoms
Time frame: Assessed at Baseline (day 0), Midpoint (day 8), and Endpoint (day 15)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Schizophreniform 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 13 inclusion and 14 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 19 Apr 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. 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?
Yes. Results are posted in the registry (first posted 29 Jan 2019). 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?
Cognitive Performance (time frame: For within-group comparisons, scores at V13 (day 15) and V14 (follow-up two weeks after V13) were compared to baseline). 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 19 Apr 2023.