Schizo Affective Disorder, Schizophrenia
Conditions
Keywords
tACS, Sham, Auditory Hallucinations, Schizophrenia, Schizo Affective Disorder, EEG
Brief summary
Investigating the effects of non-invasive transcranial alternating current stimulation (tACS) as a treatment for auditory hallucinations in patients with schizophrenia.
Detailed description
The investigator's primary objective is to provide further evidence for the effectiveness of transcranial alternating current stimulation (tACS) to treat auditory hallucinations and to collect preliminary data on whether maintenance stimulation sessions can prolong the duration of stimulation-induced clinical benefits. The investigators will be looking into effects of tACS to re-normalize pathological alpha oscillations in the dorso-lateral prefrontal cortex (dl-PFC) of patients with schizophrenia or schizo-affective disorder by comparing Auditory Hallucination Rating Scale (AHRS) scores immediately before the first stimulation session, immediately after the last stimulation session, and at the end of the 8 weeks of maintenance sessions. As a secondary objective, the investigators will assess the differential clinical effects of active sham and 10Hz tACS on electroencephalogram (EEG) measures of alpha oscillations. The investigators will also be using source localization techniques in EEG analysis, based on individual locations of the scalp electrodes and anatomical structures with the use of structural magnetic resonance imaging (sMRI).
Interventions
DEVICEtACS treatment week
10 Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 20 minutes twice for 5 consecutive days.
DEVICEtACS sham week
10Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 10 seconds twice a day for 5 consecutive days.
DEVICEMaintenance tACS
10 Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes once a weekly for 8 weeks.
DEVICEMaintenance Sham tACS
10Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 10 seconds once a week for 8 weeks.
Sponsors
National Institute of Mental Health (NIMH)
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is a double blind, randomized clinical trial.
Intervention model description
Participants will initially be randomized to either sham or 10 Hz tACS for the 5 consecutive days of stimulation. Participants will then be re-randomized to either sham or 10 Hz tACS for the 8 weeks of maintenance stimulation.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* DSM-IV diagnosis of schizophrenia, any subtype, or schizoaffective disorder with refractory hallucinations. Duration of illness \>1 year * 18 - 70 years old * Clinical stable for at least 12 weeks i.e. not requiring any hospitalization or a change in level of care * On current antipsychotic doses for at least 4 weeks * Experience at least 3 auditory hallucinations per week * Stable auditory hallucinations as demonstrated by having less than or equal to 20% change in AHRS scores across a 2 week interval during the screening period * Capacity to understand all relevant risks and potential benefits of the study and to provide written informed consent, OR has a legal guardian who can provide the informed consent on the patient's behalf with the patient providing written assent to participate
Exclusion criteria
* DSM-IV diagnosis of alcohol or substance abuse (other than nicotine) within the last month or a DSM-IV diagnosis of alcohol or substance dependence (other than nicotine) within the last 6 months * Positive urine test of cannabis, cocaine, amphetamine, barbiturates, opiates * Current treatment (within 4 weeks) with psychotropic agents including benzodiazepines that are taken on a daily basis (limit prn use to greater than 48 hours before participating in a study session) * Medical or neurological illness (unstable cardiac disease, AIDS, malignancy, liver or renal impairment) or treatment for a medical disorder that could interfere with study participation * history of traumatic brain injury that required subsequent cognitive rehabilitation, or caused cognitive sequelae * A difference of greater than 20% in AHRS scores between screening visits * Prior brain surgery * Any brain devices/implants, including cochlear implants and aneurysm clips * Co-morbid neurological condition (e.g. seizure disorder, brain tumor) * Non English speakers * Female participants who are pregnant, nursing, or unwilling to use appropriate birth control measures during study participation * Anything that, in the opinion of the investigator, would place the participant at increased risk or preclude the participants' full compliance with or completion of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Auditory Hallucination Rating Scale (AHRS) Score | Baseline, immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation. | The Auditory Hallucination Rating Scale (AHRS) measures the severity of auditory hallucinations in the past week. The scale assess 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brief Assessment Cognition in Schizophrenia (BACS) | Baseline, immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation. | The Brief Assessment of Cognition in Schizophrenia (BACS) is a clinically administered pen- and -paper battery of neurocognitive tests. The tasks administered in person included verbal memory, digit sequencing, token motor task, semantic fluency, letter fluency, symbol coding, and the tower of London task. The scores on each subtest were not normalized or scaled, values from each test were summed. In this sample the total summed scores ranged 112-296 with a standard deviation of 39.61. Higher values represent greater cognitive performance. |
| Percentage of Signal Change in the Average Alpha Oscillation Power From Eyes-Open Resting State Electroencephalogram (EEG) | Change from baseline to immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation. | Eyes-open but at rest EEG data was sampled using a 128-channel Geodesic EEG system. Alpha power spectral density was estimated using the Welch's method (in 2s Hamming windows with 0.5s overlap and 0.1 Hz spectral resolution). Aperiodic components were removed before extracting the individual alpha frequency (IAF; peak with the highest power density between 7 to 12 Hz, with consistent presence during the eyes-open blocks across all sessions). All spectra were visually inspected to confirm IAF choice. We computed the percent signal change of alpha power for each session relative to the baseline session:% change\_n=(P\_baseline-P\_n)/P\_baseline where P\_n is the alpha power in the n-th session, and P\_baseline is the alpha power in the baseline session. |
| Average Score on the Positive and Negative Syndrome Scales (PANSS) | Baseline, immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation. | The Positive and Negative Syndrome Scale (PANSS) is a 30-item clinician-administered scale. Each item is scored on a seven point scale, representing increasing levels of psychopathology (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme). Each item is rated in consultation with the definitions and criteria provided in the manual. Seven items constitute the positive scale, seven items make up the negative scale, and the remaining sixteen make up a general psychopathology scale. Therefore, the potential ranges are 7 to 49 for both positive and negative scales, and 16 to 112 for the General Psychopathology Scale. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Brief Assessment Cognition in Schizophrenia (BACS) | Change from Baseline BACS at final maintenance stimulation session. | The investigators will compare the BACS scores from baseline across the 8 weeks of maintenance stimulation sessions as an outcome measure. |
| Electroencephalogram (EEG) Auditory Task | Change across time from baseline measurement to final maintenance stimulation | 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 1st, 3rd, and final maintenance stimulation visits. |
| Auditory Hallucination Rating Scale (AHRS) | Change from Baseline AHRS at final maintenance stimulation session. | The investigators will compare the AHRS scores from baseline across the 8 weeks of maintenance stimulation sessions as an outcome measure. |
| Positive and Negative Syndrome Scale (PANSS) | Change from Baseline PANSS at final maintenance stimulation session. | The investigators will compare the PANSS scores from baseline across the 8 weeks of maintenance stimulation sessions as an outcome measure. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| tACS Treatment & tACS Maintenance 10 Hz (alpha) tACS with a peak-to-peak amplitude of 2 mA for 20 minutes twice daily during 5 consecutive days of stimulation. 10 Hz (alpha) tACS with a peak-to-peak amplitude of 2 mA for 40 minutes once weekly for 8 weeks of maintenance stimulation.
tACS treatment week: 10 Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 20 minutes twice for 5 consecutive days.
Maintenance tACS: 10 Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes once a weekly for 8 weeks. | 8 |
| Sham tACS Treatment & Sham tACS Maintenance 10 seconds of ramp in to 1 minute of 10 Hz (alpha) tACS with a ramp out of 10 seconds for a total of 80 seconds of stimulation twice daily during 5 consecutive days of stimulation. 10 seconds of ramp in to 1 minute of 10 Hz (alpha) tACS with a ramp out of 10 seconds for a total of 80 seconds of stimulation once weekly for 8 weeks of maintenance stimulation.
tACS sham week: 10Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 10 seconds twice a day for 5 consecutive days.
Maintenance Sham tACS: 10Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 10 seconds once a week for 8 weeks. | 6 |
| Sham tACS Treatment & tACS Maintenance 10 seconds of ramp in to 1 minute of 10 Hz (alpha) tACS with a ramp out of 10 seconds for a total of 80 seconds of stimulation twice daily during 5 consecutive days of stimulation. 10 Hz (alpha) tACS with a peak-to-peak amplitude of 2 mA for 40 minutes once weekly for 8 weeks of maintenance stimulation.
tACS sham week: 10Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 10 seconds twice a day for 5 consecutive days.
Maintenance tACS: 10 Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes once a weekly for 8 weeks. | 5 |
| tACS Treatment & Sham tACS Maintenance 10 Hz (alpha) tACS with a peak-to-peak amplitude of 2 mA for 20 minutes twice daily during 5 consecutive days of stimulation. 10 seconds of ramp in to 1 minute of 10 Hz (alpha) tACS with a ramp out of 10 seconds for a total of 80 seconds of stimulation once weekly for 8 weeks of maintenance stimulation.
tACS treatment week: 10 Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 20 minutes twice for 5 consecutive days.
Maintenance Sham tACS: 10Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 10 seconds once a week for 8 weeks. | 6 |
| Total | 25 |
Baseline characteristics
| Characteristic | tACS Treatment & tACS Maintenance | Total | tACS Treatment & Sham tACS Maintenance | Sham tACS Treatment & tACS Maintenance | Sham tACS Treatment & Sham tACS Maintenance |
|---|---|---|---|---|---|
| Age, Continuous | 37.4 years STANDARD_DEVIATION 12.5 | 39.2 years STANDARD_DEVIATION 11.8 | 40.4 years STANDARD_DEVIATION 11.7 | 34.2 years STANDARD_DEVIATION 10.1 | 45.0 years STANDARD_DEVIATION 9.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 20 Participants | 5 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 12 Participants | 3 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 9 Participants | 2 Participants | 0 Participants | 3 Participants |
| Region of Enrollment United States | 8 Participants | 25 Participants | 6 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Female | 3 Participants | 9 Participants | 2 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 16 Participants | 4 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 3 / 8 | 0 / 6 | 1 / 5 | 0 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 5 | 0 / 6 |
Outcome results
Primary
Mean Auditory Hallucination Rating Scale (AHRS) Score
The Auditory Hallucination Rating Scale (AHRS) measures the severity of auditory hallucinations in the past week. The scale assess 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.
Time frame: Baseline, immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation.
Population: Data for missing sessions was carried forward by replacing with the most recently completed session values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| tACS Treatment & tACS Maintenance | Mean Auditory Hallucination Rating Scale (AHRS) Score | Baseline (T1) | 25.00 score on a scale | Standard Deviation 7.37 |
| tACS Treatment & tACS Maintenance | Mean Auditory Hallucination Rating Scale (AHRS) Score | End of Maintenance | 23.94 score on a scale | Standard Deviation 9.63 |
| tACS Treatment & tACS Maintenance | Mean Auditory Hallucination Rating Scale (AHRS) Score | End of 5-Day Treatment Week | 25.13 score on a scale | Standard Deviation 8.01 |
| Sham tACS Treatment & Sham tACS Maintenance | Mean Auditory Hallucination Rating Scale (AHRS) Score | Baseline (T1) | 23.17 score on a scale | Standard Deviation 7.03 |
| Sham tACS Treatment & Sham tACS Maintenance | Mean Auditory Hallucination Rating Scale (AHRS) Score | End of Maintenance | 17.58 score on a scale | Standard Deviation 7.1 |
| Sham tACS Treatment & Sham tACS Maintenance | Mean Auditory Hallucination Rating Scale (AHRS) Score | End of 5-Day Treatment Week | 21.00 score on a scale | Standard Deviation 5.93 |
| Sham tACS Treatment & tACS Maintenance | Mean Auditory Hallucination Rating Scale (AHRS) Score | End of 5-Day Treatment Week | 25.60 score on a scale | Standard Deviation 6.84 |
| Sham tACS Treatment & tACS Maintenance | Mean Auditory Hallucination Rating Scale (AHRS) Score | Baseline (T1) | 23.40 score on a scale | Standard Deviation 6.54 |
| Sham tACS Treatment & tACS Maintenance | Mean Auditory Hallucination Rating Scale (AHRS) Score | End of Maintenance | 26.40 score on a scale | Standard Deviation 6.82 |
| tACS Treatment & Sham tACS Maintenance | Mean Auditory Hallucination Rating Scale (AHRS) Score | Baseline (T1) | 19.00 score on a scale | Standard Deviation 6.75 |
| tACS Treatment & Sham tACS Maintenance | Mean Auditory Hallucination Rating Scale (AHRS) Score | End of Maintenance | 15.67 score on a scale | Standard Deviation 4.97 |
| tACS Treatment & Sham tACS Maintenance | Mean Auditory Hallucination Rating Scale (AHRS) Score | End of 5-Day Treatment Week | 19.83 score on a scale | Standard Deviation 5.08 |
p-value: 0.66t-test, 1 sided
Secondary
Average Score on the Positive and Negative Syndrome Scales (PANSS)
The Positive and Negative Syndrome Scale (PANSS) is a 30-item clinician-administered scale. Each item is scored on a seven point scale, representing increasing levels of psychopathology (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme). Each item is rated in consultation with the definitions and criteria provided in the manual. Seven items constitute the positive scale, seven items make up the negative scale, and the remaining sixteen make up a general psychopathology scale. Therefore, the potential ranges are 7 to 49 for both positive and negative scales, and 16 to 112 for the General Psychopathology Scale.
Time frame: Baseline, immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation.
Population: Data for missing sessions was carried forward by replacing with the most recently completed session values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Positive Symptoms Scale after 8 weeks of stimulation | 18.3 score on a scale | Standard Deviation 3.9 |
| tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean General Psychopathology Symptoms Scale after 5 days of stimulation | 32.0 score on a scale | Standard Deviation 8.4 |
| tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean General Psychopathology Symptoms Scale after 8 weeks of stimulation | 32.5 score on a scale | Standard Deviation 5.8 |
| tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Positive Symptoms Scale after 5 days of stimulation | 18.6 score on a scale | Standard Deviation 4 |
| tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean General Psychopathology Symptoms Scale at Baseline | 36.5 score on a scale | Standard Deviation 11.5 |
| tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Negative Symptoms Scale at Baseline | 16.1 score on a scale | Standard Deviation 6.3 |
| tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Negative Symptoms Scale after 8 weeks of stimulation | 16.3 score on a scale | Standard Deviation 5.3 |
| tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Negative Symptoms Scale after 5 days of stimulation | 15.5 score on a scale | Standard Deviation 5.1 |
| tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Positive Symptoms Scale at Baseline | 19.5 score on a scale | Standard Deviation 4.4 |
| Sham tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Negative Symptoms Scale after 5 days of stimulation | 17.7 score on a scale | Standard Deviation 3.5 |
| Sham tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Positive Symptoms Scale after 8 weeks of stimulation | 15.7 score on a scale | Standard Deviation 5.2 |
| Sham tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean General Psychopathology Symptoms Scale after 5 days of stimulation | 29.7 score on a scale | Standard Deviation 10.3 |
| Sham tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Negative Symptoms Scale at Baseline | 18.2 score on a scale | Standard Deviation 5.3 |
| Sham tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Positive Symptoms Scale at Baseline | 16.8 score on a scale | Standard Deviation 5.4 |
| Sham tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean General Psychopathology Symptoms Scale at Baseline | 31.0 score on a scale | Standard Deviation 11.6 |
| Sham tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean General Psychopathology Symptoms Scale after 8 weeks of stimulation | 28.8 score on a scale | Standard Deviation 11 |
| Sham tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Negative Symptoms Scale after 8 weeks of stimulation | 15.5 score on a scale | Standard Deviation 5 |
| Sham tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Positive Symptoms Scale after 5 days of stimulation | 17.3 score on a scale | Standard Deviation 5.2 |
| Sham tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Negative Symptoms Scale after 5 days of stimulation | 17.6 score on a scale | Standard Deviation 6.5 |
| Sham tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Positive Symptoms Scale at Baseline | 18.0 score on a scale | Standard Deviation 2.7 |
| Sham tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Negative Symptoms Scale at Baseline | 16.8 score on a scale | Standard Deviation 4.2 |
| Sham tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean General Psychopathology Symptoms Scale at Baseline | 33.0 score on a scale | Standard Deviation 5 |
| Sham tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Positive Symptoms Scale after 5 days of stimulation | 16.6 score on a scale | Standard Deviation 3.4 |
| Sham tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean General Psychopathology Symptoms Scale after 5 days of stimulation | 22.6 score on a scale | Standard Deviation 2.4 |
| Sham tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Positive Symptoms Scale after 8 weeks of stimulation | 17.2 score on a scale | Standard Deviation 2.17 |
| Sham tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Negative Symptoms Scale after 8 weeks of stimulation | 16.8 score on a scale | Standard Deviation 4.4 |
| Sham tACS Treatment & tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean General Psychopathology Symptoms Scale after 8 weeks of stimulation | 31.20 score on a scale | Standard Deviation 2.5 |
| tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Positive Symptoms Scale after 8 weeks of stimulation | 17.0 score on a scale | Standard Deviation 3.2 |
| tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Positive Symptoms Scale after 5 days of stimulation | 17.2 score on a scale | Standard Deviation 4.7 |
| tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean General Psychopathology Symptoms Scale at Baseline | 27.7 score on a scale | Standard Deviation 7.1 |
| tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean General Psychopathology Symptoms Scale after 8 weeks of stimulation | 25.3 score on a scale | Standard Deviation 5.4 |
| tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Negative Symptoms Scale after 8 weeks of stimulation | 15.7 score on a scale | Standard Deviation 6.8 |
| tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Negative Symptoms Scale at Baseline | 13.8 score on a scale | Standard Deviation 5.7 |
| tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean General Psychopathology Symptoms Scale after 5 days of stimulation | 26.0 score on a scale | Standard Deviation 5.7 |
| tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Negative Symptoms Scale after 5 days of stimulation | 15.0 score on a scale | Standard Deviation 7 |
| tACS Treatment & Sham tACS Maintenance | Average Score on the Positive and Negative Syndrome Scales (PANSS) | Mean Positive Symptoms Scale at Baseline | 19.0 score on a scale | Standard Deviation 6.8 |
Secondary
Brief Assessment Cognition in Schizophrenia (BACS)
The Brief Assessment of Cognition in Schizophrenia (BACS) is a clinically administered pen- and -paper battery of neurocognitive tests. The tasks administered in person included verbal memory, digit sequencing, token motor task, semantic fluency, letter fluency, symbol coding, and the tower of London task. The scores on each subtest were not normalized or scaled, values from each test were summed. In this sample the total summed scores ranged 112-296 with a standard deviation of 39.61. Higher values represent greater cognitive performance.
Time frame: Baseline, immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation.
Population: Data for missing sessions was carried forward by replacing with the most recently completed session values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| tACS Treatment & tACS Maintenance | Brief Assessment Cognition in Schizophrenia (BACS) | Mean BACS at Baseline | 194.63 units on a scale | Standard Deviation 34.45 |
| tACS Treatment & tACS Maintenance | Brief Assessment Cognition in Schizophrenia (BACS) | Mean BACS after 8 weeks of stimulation | 210.00 units on a scale | Standard Deviation 52.21 |
| tACS Treatment & tACS Maintenance | Brief Assessment Cognition in Schizophrenia (BACS) | Mean BACS after five days of stimulation | 208.38 units on a scale | Standard Deviation 44.75 |
| Sham tACS Treatment & Sham tACS Maintenance | Brief Assessment Cognition in Schizophrenia (BACS) | Mean BACS at Baseline | 184.00 units on a scale | Standard Deviation 31.82 |
| Sham tACS Treatment & Sham tACS Maintenance | Brief Assessment Cognition in Schizophrenia (BACS) | Mean BACS after 8 weeks of stimulation | 194.83 units on a scale | Standard Deviation 24.2 |
| Sham tACS Treatment & Sham tACS Maintenance | Brief Assessment Cognition in Schizophrenia (BACS) | Mean BACS after five days of stimulation | 188.17 units on a scale | Standard Deviation 22.14 |
| Sham tACS Treatment & tACS Maintenance | Brief Assessment Cognition in Schizophrenia (BACS) | Mean BACS after five days of stimulation | 243.20 units on a scale | Standard Deviation 45.1 |
| Sham tACS Treatment & tACS Maintenance | Brief Assessment Cognition in Schizophrenia (BACS) | Mean BACS at Baseline | 220.40 units on a scale | Standard Deviation 39.51 |
| Sham tACS Treatment & tACS Maintenance | Brief Assessment Cognition in Schizophrenia (BACS) | Mean BACS after 8 weeks of stimulation | 235.40 units on a scale | Standard Deviation 49.2 |
| tACS Treatment & Sham tACS Maintenance | Brief Assessment Cognition in Schizophrenia (BACS) | Mean BACS at Baseline | 215.00 units on a scale | Standard Deviation 25.91 |
| tACS Treatment & Sham tACS Maintenance | Brief Assessment Cognition in Schizophrenia (BACS) | Mean BACS after 8 weeks of stimulation | 220.17 units on a scale | Standard Deviation 30.93 |
| tACS Treatment & Sham tACS Maintenance | Brief Assessment Cognition in Schizophrenia (BACS) | Mean BACS after five days of stimulation | 208.33 units on a scale | Standard Deviation 48.7 |
Secondary
Percentage of Signal Change in the Average Alpha Oscillation Power From Eyes-Open Resting State Electroencephalogram (EEG)
Eyes-open but at rest EEG data was sampled using a 128-channel Geodesic EEG system. Alpha power spectral density was estimated using the Welch's method (in 2s Hamming windows with 0.5s overlap and 0.1 Hz spectral resolution). Aperiodic components were removed before extracting the individual alpha frequency (IAF; peak with the highest power density between 7 to 12 Hz, with consistent presence during the eyes-open blocks across all sessions). All spectra were visually inspected to confirm IAF choice. We computed the percent signal change of alpha power for each session relative to the baseline session:% change\_n=(P\_baseline-P\_n)/P\_baseline where P\_n is the alpha power in the n-th session, and P\_baseline is the alpha power in the baseline session.
Time frame: Change from baseline to immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation.
Population: Data for missing sessions was carried forward by replacing with the most recently completed session values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| tACS Treatment & tACS Maintenance | Percentage of Signal Change in the Average Alpha Oscillation Power From Eyes-Open Resting State Electroencephalogram (EEG) | Average alpha power change from baseline to after 5 days of consecutive stimulation. | 1.64 percentage of signal change | Standard Deviation 22.77 |
| tACS Treatment & tACS Maintenance | Percentage of Signal Change in the Average Alpha Oscillation Power From Eyes-Open Resting State Electroencephalogram (EEG) | Average alpha power change from baseline to after the final stimulation session at week 8. | 31.35 percentage of signal change | Standard Deviation 57.06 |
| Sham tACS Treatment & Sham tACS Maintenance | Percentage of Signal Change in the Average Alpha Oscillation Power From Eyes-Open Resting State Electroencephalogram (EEG) | Average alpha power change from baseline to after the final stimulation session at week 8. | 4.40 percentage of signal change | Standard Deviation 24.94 |
| Sham tACS Treatment & Sham tACS Maintenance | Percentage of Signal Change in the Average Alpha Oscillation Power From Eyes-Open Resting State Electroencephalogram (EEG) | Average alpha power change from baseline to after 5 days of consecutive stimulation. | 4.48 percentage of signal change | Standard Deviation 41.82 |
| Sham tACS Treatment & tACS Maintenance | Percentage of Signal Change in the Average Alpha Oscillation Power From Eyes-Open Resting State Electroencephalogram (EEG) | Average alpha power change from baseline to after 5 days of consecutive stimulation. | -11.64 percentage of signal change | Standard Deviation 21 |
| Sham tACS Treatment & tACS Maintenance | Percentage of Signal Change in the Average Alpha Oscillation Power From Eyes-Open Resting State Electroencephalogram (EEG) | Average alpha power change from baseline to after the final stimulation session at week 8. | -22.21 percentage of signal change | Standard Deviation 14.7 |
| tACS Treatment & Sham tACS Maintenance | Percentage of Signal Change in the Average Alpha Oscillation Power From Eyes-Open Resting State Electroencephalogram (EEG) | Average alpha power change from baseline to after 5 days of consecutive stimulation. | 18.62 percentage of signal change | Standard Deviation 35.98 |
| tACS Treatment & Sham tACS Maintenance | Percentage of Signal Change in the Average Alpha Oscillation Power From Eyes-Open Resting State Electroencephalogram (EEG) | Average alpha power change from baseline to after the final stimulation session at week 8. | 40.96 percentage of signal change | Standard Deviation 50.4 |
Other Pre-specified
Auditory Hallucination Rating Scale (AHRS)
The investigators will compare the AHRS scores from baseline across the 8 weeks of maintenance stimulation sessions as an outcome measure.
Time frame: Change from Baseline AHRS at final maintenance stimulation session.
Other Pre-specified
Brief Assessment Cognition in Schizophrenia (BACS)
The investigators will compare the BACS scores from baseline across the 8 weeks of maintenance stimulation sessions as an outcome measure.
Time frame: Change from Baseline BACS at final maintenance stimulation session.
Other Pre-specified
Electroencephalogram (EEG) Auditory Task
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 1st, 3rd, and final maintenance stimulation visits.
Time frame: Change across time from baseline measurement to final maintenance stimulation
Other Pre-specified
Positive and Negative Syndrome Scale (PANSS)
The investigators will compare the PANSS scores from baseline across the 8 weeks of maintenance stimulation sessions as an outcome measure.
Time frame: Change from Baseline PANSS at final maintenance stimulation session.