STILL3: Targeting Auditory Hallucinations With Alternating Current Stimulation
Sponsor
University of North Carolina, Chapel Hill (Other)
Overall Status
Completed
CT.gov ID
NCT03221270
Collaborator
National Institute of Mental Health (NIMH) (NIH)
25
1
4
37.7
0.7
Study Details
Study Description
Brief Summary
Investigating the effects of non-invasive transcranial alternating current stimulation (tACS) as a treatment for auditory hallucinations in patients with schizophrenia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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).
Study Design
Study Type:
Interventional
Actual Enrollment
:
25 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
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.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.
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
This is a double blind, randomized clinical trial.
Primary Purpose:
Treatment
Official Title:
Targeting Auditory Hallucinations With Alternating Current Stimulation
Actual Study Start Date
:
Nov 14, 2017
Actual Primary Completion Date
:
Jan 5, 2021
Actual Study Completion Date
:
Jan 5, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Device: 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.
Other Names:
Device: 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.
Other Names:
|
| Sham Comparator: 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. |
Device: 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.
Other Names:
Device: 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.
Other Names:
|
| Other: Sham tACS Treatment & tACS Maintenance 10 Hz (alpha) tACS with a peak-to-peak amplitude of 2 mA for 40 minutes once weekly for 8 weeks of maintenance 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. |
Device: 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.
Other Names:
Device: 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.
Other Names:
|
| Other: 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. |
Device: 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.
Other Names:
Device: 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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
Other Outcome Measures
- 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UNC Chapel Hill | Chapel Hill | North Carolina | United States | 27599 |
Sponsors and Collaborators
- University of North Carolina, Chapel Hill
- National Institute of Mental Health (NIMH)
Investigators
- Principal Investigator: Flavio Frohlich, PhD, University of North Carolina at Chapel Hill - Department of Psychiatry
Study Documents (Full-Text)
More Information
Publications
- 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. Erratum in: Am J Psychiatry. 2012 Dec 1;169(12):1321.
- Fröhlich F, Burrello TN, Mellin JM, Cordle AL, Lustenberger CM, Gilmore JH, Jarskog LF. Exploratory study of once-daily transcranial direct current stimulation (tDCS) as a treatment for auditory hallucinations in schizophrenia. Eur Psychiatry. 2016 Mar;33:54-60. doi: 10.1016/j.eurpsy.2015.11.005. Epub 2016 Feb 8.
Responsible Party:
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT03221270
Other Study ID Numbers:
- 17-1364
- 4R33MH105574-03
First Posted:
Jul 18, 2017
Last Update Posted:
Feb 16, 2022
Last Verified:
Jan 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
Yes
Keywords provided by University of North Carolina, Chapel Hill
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | tACS Treatment & tACS Maintenance | Sham tACS Treatment & Sham tACS Maintenance | Sham tACS Treatment & tACS Maintenance | tACS Treatment & Sham tACS Maintenance |
|---|---|---|---|---|
| Arm/Group Description | 10 Hz (alpha) transcranial alternating current stimulation (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. | 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. | 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. | 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. |
| Period Title: Overall Study | ||||
| STARTED | 8 | 6 | 5 | 6 |
| Completed 5-Day Treatment | 8 | 6 | 5 | 6 |
| Completed 8-Week Maintenance | 4 | 6 | 5 | 5 |
| COMPLETED | 4 | 6 | 5 | 5 |
| NOT COMPLETED | 4 | 0 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | tACS Treatment & tACS Maintenance | Sham tACS Treatment & Sham tACS Maintenance | Sham tACS Treatment & tACS Maintenance | tACS Treatment & Sham tACS Maintenance | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 8 | 6 | 5 | 6 | 25 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
37.4
(12.5)
|
45.0
(9.6)
|
34.2
(10.1)
|
40.4
(11.7)
|
39.2
(11.8)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
3
37.5%
|
2
33.3%
|
2
40%
|
2
33.3%
|
9
36%
|
| Male |
5
62.5%
|
4
66.7%
|
3
60%
|
4
66.7%
|
16
64%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
1
12.5%
|
0
0%
|
1
20%
|
0
0%
|
2
8%
|
| Not Hispanic or Latino |
5
62.5%
|
6
100%
|
4
80%
|
5
83.3%
|
20
80%
|
| Unknown or Not Reported |
2
25%
|
0
0%
|
0
0%
|
1
16.7%
|
3
12%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
1
20%
|
0
0%
|
1
4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
2
25%
|
3
50%
|
4
80%
|
3
50%
|
12
48%
|
| White |
4
50%
|
3
50%
|
0
0%
|
2
33.3%
|
9
36%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
2
25%
|
0
0%
|
0
0%
|
1
16.7%
|
3
12%
|
| Region of Enrollment (Count of Participants) | |||||
| United States |
8
100%
|
6
100%
|
5
100%
|
6
100%
|
25
100%
|
Outcome Measures
| Title | Mean Auditory Hallucination Rating Scale (AHRS) Score |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data for missing sessions was carried forward by replacing with the most recently completed session values. |
| Arm/Group Title | tACS Treatment & tACS Maintenance | Sham tACS Treatment & Sham tACS Maintenance | Sham tACS Treatment & tACS Maintenance | tACS Treatment & Sham tACS Maintenance |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 8 | 6 | 5 | 6 |
| Baseline (T1) |
25.00
(7.37)
|
23.17
(7.03)
|
23.40
(6.54)
|
19.00
(6.75)
|
| End of 5-Day Treatment Week |
25.13
(8.01)
|
21.00
(5.93)
|
25.60
(6.84)
|
19.83
(5.08)
|
| End of Maintenance |
23.94
(9.63)
|
17.58
(7.10)
|
26.40
(6.82)
|
15.67
(4.97)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | tACS Treatment & tACS Maintenance, Sham tACS Treatment & Sham tACS Maintenance, Sham tACS Treatment & tACS Maintenance, tACS Treatment & Sham tACS Maintenance |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | alternative hypothesis: true difference in means is greater than 0 | |
| Statistical Test of Hypothesis | p-Value | 0.66 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
| Estimated Value | -0.43 | |
| Confidence Interval |
(1-Sided) 95% -2.25 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Signal Change in the Average Alpha Oscillation Power From Eyes-Open Resting State Electroencephalogram (EEG) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data for missing sessions was carried forward by replacing with the most recently completed session values. |
| Arm/Group Title | tACS Treatment & tACS Maintenance | Sham tACS Treatment & Sham tACS Maintenance | Sham tACS Treatment & tACS Maintenance | tACS Treatment & Sham tACS Maintenance |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 8 | 6 | 5 | 6 |
| Average alpha power change from baseline to after 5 days of consecutive stimulation. |
1.64
(22.77)
|
4.48
(41.82)
|
-11.64
(21.00)
|
18.62
(35.98)
|
| Average alpha power change from baseline to after the final stimulation session at week 8. |
31.35
(57.06)
|
4.40
(24.94)
|
-22.21
(14.70)
|
40.96
(50.40)
|
| Title | Average Score on the Positive and Negative Syndrome Scales (PANSS) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data for missing sessions was carried forward by replacing with the most recently completed session values. |
| Arm/Group Title | tACS Treatment & tACS Maintenance | Sham tACS Treatment & Sham tACS Maintenance | Sham tACS Treatment & tACS Maintenance | tACS Treatment & Sham tACS Maintenance |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 8 | 6 | 5 | 6 |
| Mean Positive Symptoms Scale at Baseline |
19.5
(4.4)
|
16.8
(5.4)
|
18.0
(2.7)
|
19.0
(6.8)
|
| Mean Negative Symptoms Scale at Baseline |
16.1
(6.3)
|
18.2
(5.3)
|
16.8
(4.2)
|
13.8
(5.7)
|
| Mean General Psychopathology Symptoms Scale at Baseline |
36.5
(11.5)
|
31.0
(11.6)
|
33.0
(5.0)
|
27.7
(7.1)
|
| Mean Positive Symptoms Scale after 5 days of stimulation |
18.6
(4.0)
|
17.3
(5.2)
|
16.6
(3.4)
|
17.2
(4.7)
|
| Mean Negative Symptoms Scale after 5 days of stimulation |
15.5
(5.1)
|
17.7
(3.5)
|
17.6
(6.5)
|
15.0
(7.0)
|
| Mean General Psychopathology Symptoms Scale after 5 days of stimulation |
32.0
(8.4)
|
29.7
(10.3)
|
22.6
(2.4)
|
26.0
(5.7)
|
| Mean Positive Symptoms Scale after 8 weeks of stimulation |
18.3
(3.9)
|
15.7
(5.2)
|
17.2
(2.17)
|
17.0
(3.2)
|
| Mean Negative Symptoms Scale after 8 weeks of stimulation |
16.3
(5.3)
|
15.5
(5.0)
|
16.8
(4.4)
|
15.7
(6.8)
|
| Mean General Psychopathology Symptoms Scale after 8 weeks of stimulation |
32.5
(5.8)
|
28.8
(11.0)
|
31.20
(2.5)
|
25.3
(5.4)
|
| Title | Brief Assessment Cognition in Schizophrenia (BACS) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data for missing sessions was carried forward by replacing with the most recently completed session values. |
| Arm/Group Title | tACS Treatment & tACS Maintenance | Sham tACS Treatment & Sham tACS Maintenance | Sham tACS Treatment & tACS Maintenance | tACS Treatment & Sham tACS Maintenance |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 8 | 6 | 5 | 6 |
| Mean BACS at Baseline |
194.63
(34.45)
|
184.00
(31.82)
|
220.40
(39.51)
|
215.00
(25.91)
|
| Mean BACS after five days of stimulation |
208.38
(44.75)
|
188.17
(22.14)
|
243.20
(45.10)
|
208.33
(48.70)
|
| Mean BACS after 8 weeks of stimulation |
210.00
(52.21)
|
194.83
(24.20)
|
235.40
(49.20)
|
220.17
(30.93)
|
| Title | Electroencephalogram (EEG) Auditory Task |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Auditory Hallucination Rating Scale (AHRS) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Positive and Negative Syndrome Scale (PANSS) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Brief Assessment Cognition in Schizophrenia (BACS) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | Adverse events were assessed at each visit during the 5-day treatment and the 8-week maintenance over an approximate 9-week period using a stimulation side effects questionnaire provided to participants after every presentation of each intervention. Data were not collected beyond the eighth maintenance treatment week. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | tACS Treatment & tACS Maintenance | Sham tACS Treatment & Sham tACS Maintenance | Sham tACS Treatment & tACS Maintenance | tACS Treatment & Sham tACS Maintenance | ||||
| Arm/Group Description | 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. | 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. | 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. | 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. | ||||
All Cause Mortality |
||||||||
| tACS Treatment & tACS Maintenance | Sham tACS Treatment & Sham tACS Maintenance | Sham tACS Treatment & tACS Maintenance | tACS Treatment & Sham tACS Maintenance | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/8 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | ||||
Serious Adverse Events |
||||||||
| tACS Treatment & tACS Maintenance | Sham tACS Treatment & Sham tACS Maintenance | Sham tACS Treatment & tACS Maintenance | tACS Treatment & Sham tACS Maintenance | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/8 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| tACS Treatment & tACS Maintenance | Sham tACS Treatment & Sham tACS Maintenance | Sham tACS Treatment & tACS Maintenance | tACS Treatment & Sham tACS Maintenance | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/8 (37.5%) | 0/6 (0%) | 1/5 (20%) | 0/6 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Diarrhea | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Muscular Pain | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/6 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Burning Sensation on Scalp | 2/8 (25%) | 2 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Rachel Force, PhD |
|---|---|
| Organization | University of North Carolina at Chapel Hill |
| Phone | 984-974-6239 |
| rachel_force@med.unc.edu |
Responsible Party:
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT03221270
Other Study ID Numbers:
- 17-1364
- 4R33MH105574-03
First Posted:
Jul 18, 2017
Last Update Posted:
Feb 16, 2022
Last Verified:
Jan 1, 2022