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| ID | Type | Description | Link |
|---|---|---|---|
| 1R21MH105574-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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Investigating the effects of non-invasive transcranial current stimulation as a treatment for auditory hallucinations in patients with schizophrenia.
The investigator's primary objective is to conduct a pilot clinical trial to establish the feasibility and to collect first effectiveness data for the use of transcranial alternating current stimulation (tACS) to re-normalize pathological alpha oscillations in dorso-lateral prefrontal cortex (dl-PFC) of patients with schizophrenia or schizoaffective disorder by comparing Auditory Hallucination Rating Scale (AHRS) scores immediately before the first stimulation session and immediately after the last stimulation session. As a secondary objective the investigators will assess the differential clinical effects of sham, 10 Hz and 2 mA transcranial direct current stimulation (tDCS) on electroencephalogram (EEG) measures of alpha oscillations.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| tACS (alpha) | Experimental | 20 participants: 10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily |
|
| tDCS | Experimental | 20 participants: 2mA stimulation for 20 minutes twice daily |
|
| Sham stimulation | Sham Comparator | 20 participants: Will include 10 seconds of ramp in to 1 minutes of 10 Hz tACS with a ramp out of 10 seconds for a total of 80 seconds of stimulation twice daily. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tACS (alpha) | Device |
| ||
| tDCS |
| Measure | Description | Time Frame |
|---|---|---|
| Proportional Change From Baseline in Auditory Hallucination Rating Scale (AHRS) Score | The Auditory Hallucination Rating Scale (AHRS) measures the severity of auditory hallucinations in the past week. The scale assesses frequency, duration, location, loudness, belief of origin of voices, negative content, distress, disruption to life, and control over voices. All items are measured on a scale of 0 to 4, with a total possible score of 44. Higher scores indicate higher severity of auditory hallucinations. The investigators will compare the AHRS scores from immediately before the first stimulation and immediately after the last stimulation session as the investigator's primary outcomes measure. | Baseline, five days post baseline, 2 weeks post baseline, 5 weeks post baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Alpha Oscillations Measured With Electroencephalogram (EEG) Resting State From Baseline | The investigators will compare alpha oscillation power from resting state EEG recordings on the first and last day of stimulation. The investigators will also collect EEG recordings data at the one week and one month follow up visits. The investigators will use each of the four EEG recordings as data to analyze alpha frequency activity as a pilot study for derivation of EEG biomarkers. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Electroencephalogram (EEG) Auditory Tasks: Oddball Task From Baseline | The investigators will compare auditory responses during auditory tasks EEG recordings on the first and last day of stimulation. The investigators will also collect EEG recordings data at the one week and one month follow up visits. The investigators will use each of the four EEG recordings as data to analyze alpha frequency activity as a pilot study for derivation of EEG biomarkers and look for increase in auditory responses. Auditory oddball paradigm is an experimental design that has standard (low-pitch) and deviant (high-pitch) stimuli. Differences in ERP from these two stimuli can measure functions of sensory processing. Patients with schizophrenia often exhibit abnormal responses to the stimuli thus its discrepancy compared to healthy human participants can be a hallmark of symptoms in schizophrenia. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Flavio Frohlich, PhD | University of North Carolina at Chapel Hill - Department of Psychiatry | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UNC Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22581236 | Background | Brunelin J, Mondino M, Gassab L, Haesebaert F, Gaha L, Suaud-Chagny MF, Saoud M, Mechri A, Poulet E. Examining transcranial direct-current stimulation (tDCS) as a treatment for hallucinations in schizophrenia. Am J Psychiatry. 2012 Jul;169(7):719-24. doi: 10.1176/appi.ajp.2012.11071091. |
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Participants randomly assigned to 1 of 3 arms, tDCS, tACS, or active sham. tDCS, tACS current delivered during awake, resting state for 20 minutes twice daily on 5 consecutive days. Sham stimulation was delivered for equal period of time and number of sessions. 33 participants signed consent, 7 screen fails, 1 withdrew.
Participants recruited through medical providers or ads. Providers knew study criteria and discussed the study with patients during regular appointments. Interested participants contacted the study team, or were contacted by study team. Participants recruited from STEP clinic, Chapel Hill and Raleigh, and local clinics. Recruitment 4/15 to 12/16.
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| ID | Title | Description |
|---|---|---|
| FG000 | tACS (Alpha) | 10Hz transcranial alternating current stimulation (tACS) at the alpha frequency with a peak-to-peak amplitude of 2mA for 20 minutes twice daily tACS (alpha) |
| FG001 | tDCS | 2mA transcranial direct current stimulation (tDCS) for 20 minutes twice daily |
| FG002 | Sham Stimulation | Will include 10 seconds of ramp in to 1 minutes of 10 Hz tACS with a ramp out of 10 seconds for a total of 80 seconds of stimulation twice daily. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | tACS (Alpha) | 10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily tACS (alpha) |
| BG001 | tDCS | 2mA stimulation for 20 minutes twice daily tDCS |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Proportional Change From Baseline in Auditory Hallucination Rating Scale (AHRS) Score | The Auditory Hallucination Rating Scale (AHRS) measures the severity of auditory hallucinations in the past week. The scale assesses frequency, duration, location, loudness, belief of origin of voices, negative content, distress, disruption to life, and control over voices. All items are measured on a scale of 0 to 4, with a total possible score of 44. Higher scores indicate higher severity of auditory hallucinations. The investigators will compare the AHRS scores from immediately before the first stimulation and immediately after the last stimulation session as the investigator's primary outcomes measure. | Per protocol; All eligible participants who completed every session of the study from the initial session through the one month follow-up that followed study protocol. | Posted | Mean | Standard Deviation | proportion to baseline | Baseline, five days post baseline, 2 weeks post baseline, 5 weeks post baseline |
|
Adverse events data collected from the beginning of the study (6/2015) through the completion of the study (2/2017) for a total of 20 months.
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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 | tACS (Alpha) | 10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily tACS (alpha) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Flavio Frohlich | University of North Carolina at Chapel Hill | (919) 966-4584 | flavio_frohlich@med.unc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 29, 2015 | Jan 25, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D011618 | Psychotic Disorders |
| D006212 | Hallucinations |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
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| ID | Term |
|---|---|
| D065908 | Transcranial Direct Current Stimulation |
| ID | Term |
|---|---|
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
| D003295 | Convulsive Therapy |
| D013000 | Psychiatric Somatic Therapies |
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|
| Baseline, five days post baseline |
| Change in Positive and Negative Syndrome Scale (PANSS) Scores | The investigators will compare the PANSS total scores immediately before first stimulation session and immediately after last stimulation session as secondary outcome measures. Scores range from 30 to 210, with higher scores indicating more severe symptomology. | baseline, five days post baseline, five weeks post baseline |
| Change in Brief Assessment of Cognition in Schizophrenia (BACS) Score | The Brief Assessment of Cognition in Schizophrenia (BACS) is a battery of cognitive assessments assessing verbal memory and learning, working memory, motor function, verbal fluency, speed of processing, and executive function. Higher scores indicate better cognitive performance. The investigators will compare the BACS total scores immediately before first stimulation session and immediately after last stimulation session as secondary outcome measures. Verbal Memory: Score out of 75 Digit Sequencing: Score out of 28 Token Motor: Score out of 100 Fluency: No score limit Symbol Coding: Score out of 110 Tower of London: Score out of 22 Reported score is the mean of these 6 subtests. Healthy controls (Keefe et al., 2006) scored 45.6 as a comparison. | baseline, five days post baseline, five weeks post baseline |
| Change in Peak Frequency of Functional Connectivity From Baseline Measured With Electroencephalogram (EEG) Resting State | The investigators will compare peak frequency of functional connectivity from resting state EEG recordings on the first and last day of stimulation. The investigators will also collect EEG recordings data at the one week and one month follow up visits. The investigators will use each of the four EEG recordings as data to analyze the change in peak frequency of functional connectivity as a pilot study for derivation of EEG biomarkers. | Baseline, five days post baseline |
| baseline, five days post baseline |
| Change in Electroencephalogram (EEG) Auditory Tasks: Click Train Task From Baseline | The investigators will compare auditory responses during auditory tasks EEG recordings on the first and last day of stimulation. The investigators will also collect this data at the one week and one month follow up visits. Auditory steady-state response (ASSR) from EEG data elicited by auditory click trains is considered as a hallmark of network dysfunction in schizophrenia. To obtain ASSR, auditory tones at a specific frequency (e.g., 40Hz) are presented for multiple trials and EEG data is analyzed to extract brain responses to the stimuli. One common way to extract the brain responses from this task is phase coherence between trials. When external stimuli (click trains) occur, brain signals are synchronized to these stimuli and its coherence should be the highest at the stimulation frequency. Phase information for calculating the coherence can be obtained by time-frequency analysis. Averaged coherence across the multiple trials can represent the inter-trial phase coherence. | baseline, five days post baseline |
| Unstable symptoms during screening |
|
| BG002 | Sham Stimulation | Will include 10 seconds of ramp in to 1 minutes of 10 Hz tACS with a ramp out of 10 seconds for a total of 80 seconds of stimulation twice daily. tACS (alpha) |
| BG003 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Auditory Hallucination Rating Scale | The Auditory Hallucination Rating Scale (AHRS) measures the severity of auditory hallucinations in the past week. The scale assesses frequency, duration, location, loudness, belief of origin of voices, negative content, distress, disruption to life, and control over voices. All items are measured on a scale of 0 to 4, with a total possible score of 44. Higher scores indicate higher severity of auditory hallucinations. | Mean | Standard Deviation | units on a scale |
|
| Positive and Negative Syndrome Scale | The Positive and Negative Syndrome Scale (PANSS) is a clinical measure assessing the positive, negative, and general symptoms of psychosis. There are 30 items (7 positive, 7 negative, and 16 general). The score for each item ranges from 1 (absent) to 7 (extreme) and the PANSS total score ranges from 30 to 210, with higher scores indicating more severe symptoms. | Mean | Standard Deviation | units on a scale |
|
| Brief Assessment of Cognition in Schizophrenia | The Brief Assessment of Cognition in Schizophrenia (BACS) is a battery of cognitive assessments assessing verbal memory and learning, working memory, motor function, verbal fluency, speed of processing, and executive function. Higher scores indicate better cognitive performance. Verbal Memory: Score out of 75 Digit Sequencing: Score out of 28 Token Motor: Score out of 100 Fluency: No score limit Symbol Coding: Score out of 110 Tower of London: Score out of 22 Reported score is the mean of these 6 subtests. Healthy controls (Keefe et al., 2006) scored 45.6 as a comparison. | Mean | Standard Deviation | units on a scale |
|
| tACS (Alpha) |
10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily tACS (alpha) |
| OG001 | tDCS | 2mA stimulation for 20 minutes twice daily tDCS |
| OG002 | Sham Stimulation | Will include 10 seconds of ramp in to 1 minutes of 10 Hz tACS with a ramp out of 10 seconds for a total of 80 seconds of stimulation twice daily. tACS (alpha) |
|
|
|
| Secondary | Change in Alpha Oscillations Measured With Electroencephalogram (EEG) Resting State From Baseline | The investigators will compare alpha oscillation power from resting state EEG recordings on the first and last day of stimulation. The investigators will also collect EEG recordings data at the one week and one month follow up visits. The investigators will use each of the four EEG recordings as data to analyze alpha frequency activity as a pilot study for derivation of EEG biomarkers. | Per protocol; All eligible participants who completed every session of the study from the initial session through the one month follow-up that followed the study protocol. | Posted | Mean | Standard Deviation | decibel (dB) | Baseline, five days post baseline |
|
|
|
| Secondary | Change in Positive and Negative Syndrome Scale (PANSS) Scores | The investigators will compare the PANSS total scores immediately before first stimulation session and immediately after last stimulation session as secondary outcome measures. Scores range from 30 to 210, with higher scores indicating more severe symptomology. | Per protocol; All eligible participants who completed every session of the study from the initial session through the one month follow-up that followed study protocol. | Posted | Mean | Standard Deviation | scores on a scale | baseline, five days post baseline, five weeks post baseline |
|
|
|
|
| Secondary | Change in Brief Assessment of Cognition in Schizophrenia (BACS) Score | The Brief Assessment of Cognition in Schizophrenia (BACS) is a battery of cognitive assessments assessing verbal memory and learning, working memory, motor function, verbal fluency, speed of processing, and executive function. Higher scores indicate better cognitive performance. The investigators will compare the BACS total scores immediately before first stimulation session and immediately after last stimulation session as secondary outcome measures. Verbal Memory: Score out of 75 Digit Sequencing: Score out of 28 Token Motor: Score out of 100 Fluency: No score limit Symbol Coding: Score out of 110 Tower of London: Score out of 22 Reported score is the mean of these 6 subtests. Healthy controls (Keefe et al., 2006) scored 45.6 as a comparison. | Per protocol; All eligible participants who completed every session of the study from the initial session through the one month follow-up that followed study protocol. | Posted | Mean | Standard Deviation | scores on a scale | baseline, five days post baseline, five weeks post baseline |
|
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|
|
| Other Pre-specified | Change in Electroencephalogram (EEG) Auditory Tasks: Oddball Task From Baseline | The investigators will compare auditory responses during auditory tasks EEG recordings on the first and last day of stimulation. The investigators will also collect EEG recordings data at the one week and one month follow up visits. The investigators will use each of the four EEG recordings as data to analyze alpha frequency activity as a pilot study for derivation of EEG biomarkers and look for increase in auditory responses. Auditory oddball paradigm is an experimental design that has standard (low-pitch) and deviant (high-pitch) stimuli. Differences in ERP from these two stimuli can measure functions of sensory processing. Patients with schizophrenia often exhibit abnormal responses to the stimuli thus its discrepancy compared to healthy human participants can be a hallmark of symptoms in schizophrenia. | Per protocol; All eligible participants who completed every session of the study from the initial session through the one month follow-up that followed study protocol. | Posted | Mean | Standard Deviation | micro volts | baseline, five days post baseline |
|
|
|
| Other Pre-specified | Change in Electroencephalogram (EEG) Auditory Tasks: Click Train Task From Baseline | The investigators will compare auditory responses during auditory tasks EEG recordings on the first and last day of stimulation. The investigators will also collect this data at the one week and one month follow up visits. Auditory steady-state response (ASSR) from EEG data elicited by auditory click trains is considered as a hallmark of network dysfunction in schizophrenia. To obtain ASSR, auditory tones at a specific frequency (e.g., 40Hz) are presented for multiple trials and EEG data is analyzed to extract brain responses to the stimuli. One common way to extract the brain responses from this task is phase coherence between trials. When external stimuli (click trains) occur, brain signals are synchronized to these stimuli and its coherence should be the highest at the stimulation frequency. Phase information for calculating the coherence can be obtained by time-frequency analysis. Averaged coherence across the multiple trials can represent the inter-trial phase coherence. | Per protocol; All eligible participants who completed every session of the study from the initial session through the one month follow-up that followed study protocol. | Posted | Mean | Standard Deviation | inter-trial phase coherence | baseline, five days post baseline |
|
|
|
| Secondary | Change in Peak Frequency of Functional Connectivity From Baseline Measured With Electroencephalogram (EEG) Resting State | The investigators will compare peak frequency of functional connectivity from resting state EEG recordings on the first and last day of stimulation. The investigators will also collect EEG recordings data at the one week and one month follow up visits. The investigators will use each of the four EEG recordings as data to analyze the change in peak frequency of functional connectivity as a pilot study for derivation of EEG biomarkers. | Per protocol; All eligible participants who completed every session of the study from the initial session through the one month follow-up that followed the study protocol. | Posted | Mean | Standard Deviation | Hertz (Hz) | Baseline, five days post baseline |
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|
| 0 |
| 8 |
| 0 |
| 8 |
| 0 |
| 8 |
| EG001 | tDCS | 2mA stimulation for 20 minutes twice daily tDCS | 0 | 7 | 0 | 7 | 0 | 7 |
| EG002 | Sham Stimulation | Will include 10 seconds of ramp in to 1 minutes of 10 Hz tACS with a ramp out of 10 seconds for a total of 80 seconds of stimulation twice daily. tACS (alpha) | 0 | 7 | 0 | 7 | 0 | 7 |
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| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D004191 | Behavioral Disciplines and Activities |
| D004597 | Electroshock |
| D011580 | Psychological Techniques |
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