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| Name | Class |
|---|---|
| Neuronetics | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
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| 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rTMS | Device | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 | Change from Baseline (day 1) to Visit 13 (day 15) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
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:
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
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| IU Center for NeuroImaging | Indianapolis | Indiana | 46202 | United States | ||
| Prevention and Recovery Center for Early Psychosis |
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The recruitment period for the study was from 04/2014-09/2016. Recruitment took place at the Prevention and Recovery Center for Early Psychosis, an Eskenazi Health - Midtown Mental Health Clinic and at local community mental health centers in the Indianapolis area.
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| ID | Title | Description |
|---|---|---|
| FG000 | rTMS | 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). rTMS: 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 |
| FG001 | Sham | 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). 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). Ten sessions over a two week duration |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | rTMS | 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). rTMS: 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Least Squares Mean | Standard Error | BACS Composite Score | For within-group comparisons, scores at V13 (day 15) and V14 (follow-up two weeks after V13) were compared to baseline |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | rTMS | 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). rTMS: 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Right Earache | Nervous system disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Michael Francis | IndianaU | 317-880-8495 | mmfranci@iupui.edu |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D011618 | Psychotic Disorders |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| Sham Comparator | Device | 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 |
|
|
| 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. | 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. | 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. | Assessed at Baseline (day 0), Midpoint (day 8), and Endpoint (day 15) |
| Indianapolis |
| Indiana |
| 46202 |
| United States |
| BG001 | Sham | 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). 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). Ten sessions over a two week duration |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| rTMS |
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). rTMS: 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 |
| OG001 | Sham | 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). 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). Ten sessions over a two week duration |
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| Primary | Cortical Activation | effects of rTMS on cortical activation using fMRI during working memory and episodic memory tasks | Posted | Mean | Standard Deviation | Bold signal change | Change from Baseline (day 1) to Visit 13 (day 15) |
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| Secondary | 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. | Posted | Least Squares Mean | Standard Error | seconds | 14 days |
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| Secondary | 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. | Posted | Least Squares Mean | Standard Error | BACS Sub-scale Scores | 14 days |
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| Secondary | 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. | Posted | Least Squares Mean | Standard Error | Change Scores Relative to Baseline | For within-group comparisons, scores at V13 (day 15) and V14 (follow-up two weeks after V13) were compared to baseline |
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| Secondary | 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. | Posted | Mean | Standard Deviation | NSA-16 Scores | Assessed at Baseline (day 0), Midpoint (day 8), and Endpoint (day 15) |
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| 0 |
| 10 |
| 4 |
| 10 |
| EG001 | Sham | 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). 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). Ten sessions over a two week duration | 0 | 10 | 3 | 10 |
| Headache | Nervous system disorders |
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| Gum Sensation | Nervous system disorders |
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| Muscle Twitch (post treatment) | Nervous system disorders |
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| Application Site Discomfort | Nervous system disorders |
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| Token Motor Total |
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| Semantic & Letter Fluency |
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| Symbol Coding |
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| Tower of London |
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| V13 PANSS Total Negative Score |
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| V14 PANSS Total Negative Score |
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| V13 PANSS Total Positive Score |
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| V14 PANSS Total Positive Score |
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| NSA-16 Total Endpoint Scores |
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