Trial Outcomes & Findings for STimulation to Improve Auditory haLLucinations (NCT NCT02360228)
NCT ID: NCT02360228
Last Updated: 2018-04-27
Results Overview
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.
COMPLETED
NA
25 participants
Baseline, five days post baseline, 2 weeks post baseline, 5 weeks post baseline
2018-04-27
Participant Flow
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.
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.
Participant milestones
| Measure |
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)
|
tDCS
2mA transcranial direct current stimulation (tDCS) for 20 minutes twice daily
|
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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
9
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
7
|
7
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
1
|
Reasons for withdrawal
| Measure |
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)
|
tDCS
2mA transcranial direct current stimulation (tDCS) for 20 minutes twice daily
|
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.
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
|
Overall Study
Self-discontinued medication
|
0
|
1
|
0
|
|
Overall Study
Unstable symptoms during screening
|
0
|
0
|
1
|
Baseline Characteristics
STimulation to Improve Auditory haLLucinations
Baseline characteristics by cohort
| Measure |
tACS (Alpha)
n=8 Participants
10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily
tACS (alpha)
|
tDCS
n=7 Participants
2mA stimulation for 20 minutes twice daily
tDCS
|
Sham Stimulation
n=7 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.
tACS (alpha)
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
47 years
STANDARD_DEVIATION 9.72 • n=5 Participants
|
29.75 years
STANDARD_DEVIATION 10.97 • n=7 Participants
|
38.86 years
STANDARD_DEVIATION 10.01 • n=5 Participants
|
38.86 years
STANDARD_DEVIATION 12.19 • n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=5 Participants
|
7 participants
n=7 Participants
|
7 participants
n=5 Participants
|
22 participants
n=4 Participants
|
|
Auditory Hallucination Rating Scale
|
25.88 units on a scale
STANDARD_DEVIATION 3.80 • n=5 Participants
|
23.00 units on a scale
STANDARD_DEVIATION 6.90 • n=7 Participants
|
24.71 units on a scale
STANDARD_DEVIATION 5.91 • n=5 Participants
|
24.59 units on a scale
STANDARD_DEVIATION 5.47 • n=4 Participants
|
|
Positive and Negative Syndrome Scale
|
52.75 units on a scale
STANDARD_DEVIATION 7.74 • n=5 Participants
|
58.86 units on a scale
STANDARD_DEVIATION 14.66 • n=7 Participants
|
57.00 units on a scale
STANDARD_DEVIATION 11.60 • n=5 Participants
|
56.05 units on a scale
STANDARD_DEVIATION 11.27 • n=4 Participants
|
|
Brief Assessment of Cognition in Schizophrenia
|
31.21 units on a scale
STANDARD_DEVIATION 5.68 • n=5 Participants
|
38.26 units on a scale
STANDARD_DEVIATION 9.01 • n=7 Participants
|
38.93 units on a scale
STANDARD_DEVIATION 7.17 • n=5 Participants
|
35.91 units on a scale
STANDARD_DEVIATION 7.87 • n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline, five days post baseline, 2 weeks post baseline, 5 weeks post baselinePopulation: 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.
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.
Outcome measures
| Measure |
tACS (Alpha)
n=8 Participants
10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily
tACS (alpha)
|
tDCS
n=7 Participants
2mA stimulation for 20 minutes twice daily
tDCS
|
Sham Stimulation
n=7 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.
tACS (alpha)
|
|---|---|---|---|
|
Proportional Change From Baseline in Auditory Hallucination Rating Scale (AHRS) Score
5 days from baseline
|
0.85 proportion to baseline
Standard Deviation 0.13
|
0.94 proportion to baseline
Standard Deviation 0.36
|
0.91 proportion to baseline
Standard Deviation 0.08
|
|
Proportional Change From Baseline in Auditory Hallucination Rating Scale (AHRS) Score
2 weeks from baseline
|
0.84 proportion to baseline
Standard Deviation 0.19
|
0.94 proportion to baseline
Standard Deviation 0.20
|
0.92 proportion to baseline
Standard Deviation 0.11
|
|
Proportional Change From Baseline in Auditory Hallucination Rating Scale (AHRS) Score
5 weeks from baseline
|
0.85 proportion to baseline
Standard Deviation 0.16
|
1.01 proportion to baseline
Standard Deviation 0.14
|
0.85 proportion to baseline
Standard Deviation 0.09
|
SECONDARY outcome
Timeframe: Baseline, five days post baselinePopulation: 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.
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.
Outcome measures
| Measure |
tACS (Alpha)
n=8 Participants
10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily
tACS (alpha)
|
tDCS
n=7 Participants
2mA stimulation for 20 minutes twice daily
tDCS
|
Sham Stimulation
n=7 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.
tACS (alpha)
|
|---|---|---|---|
|
Change in Alpha Oscillations Measured With Electroencephalogram (EEG) Resting State From Baseline
|
1.5 decibel (dB)
Standard Deviation 0.2
|
0.3 decibel (dB)
Standard Deviation 0.1
|
0.4 decibel (dB)
Standard Deviation 0.2
|
SECONDARY outcome
Timeframe: baseline, five days post baseline, five weeks post baselinePopulation: 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.
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.
Outcome measures
| Measure |
tACS (Alpha)
n=8 Participants
10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily
tACS (alpha)
|
tDCS
n=7 Participants
2mA stimulation for 20 minutes twice daily
tDCS
|
Sham Stimulation
n=7 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.
tACS (alpha)
|
|---|---|---|---|
|
Change in Positive and Negative Syndrome Scale (PANSS) Scores
5 days from baseline
|
51.25 scores on a scale
Standard Deviation 8.19
|
54.71 scores on a scale
Standard Deviation 11.84
|
55.29 scores on a scale
Standard Deviation 10.86
|
|
Change in Positive and Negative Syndrome Scale (PANSS) Scores
5 weeks from baseline
|
51.13 scores on a scale
Standard Deviation 9.95
|
52.86 scores on a scale
Standard Deviation 7.47
|
51.57 scores on a scale
Standard Deviation 12.20
|
SECONDARY outcome
Timeframe: baseline, five days post baseline, five weeks post baselinePopulation: 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.
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.
Outcome measures
| Measure |
tACS (Alpha)
n=8 Participants
10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily
tACS (alpha)
|
tDCS
n=7 Participants
2mA stimulation for 20 minutes twice daily
tDCS
|
Sham Stimulation
n=7 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.
tACS (alpha)
|
|---|---|---|---|
|
Change in Brief Assessment of Cognition in Schizophrenia (BACS) Score
5 days from baseline
|
31.58 scores on a scale
Standard Deviation 5.77
|
42.05 scores on a scale
Standard Deviation 10.82
|
41.50 scores on a scale
Standard Deviation 10.52
|
|
Change in Brief Assessment of Cognition in Schizophrenia (BACS) Score
5 weeks from baseline
|
29.81 scores on a scale
Standard Deviation 5.50
|
39.71 scores on a scale
Standard Deviation 9.39
|
40.83 scores on a scale
Standard Deviation 9.71
|
SECONDARY outcome
Timeframe: Baseline, five days post baselinePopulation: 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.
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.
Outcome measures
| Measure |
tACS (Alpha)
n=8 Participants
10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily
tACS (alpha)
|
tDCS
n=7 Participants
2mA stimulation for 20 minutes twice daily
tDCS
|
Sham Stimulation
n=7 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.
tACS (alpha)
|
|---|---|---|---|
|
Change in Peak Frequency of Functional Connectivity From Baseline Measured With Electroencephalogram (EEG) Resting State
|
10 Hertz (Hz)
Standard Deviation 0
|
8 Hertz (Hz)
Standard Deviation 0.5
|
11 Hertz (Hz)
Standard Deviation 0.5
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline, five days post baselinePopulation: 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.
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.
Outcome measures
| Measure |
tACS (Alpha)
n=8 Participants
10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily
tACS (alpha)
|
tDCS
n=7 Participants
2mA stimulation for 20 minutes twice daily
tDCS
|
Sham Stimulation
n=7 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.
tACS (alpha)
|
|---|---|---|---|
|
Change in Electroencephalogram (EEG) Auditory Tasks: Oddball Task From Baseline
standard tones
|
0.6 micro volts
Standard Deviation 0.1
|
0.4 micro volts
Standard Deviation 0.1
|
0.5 micro volts
Standard Deviation 0.1
|
|
Change in Electroencephalogram (EEG) Auditory Tasks: Oddball Task From Baseline
deviant tones
|
0.3 micro volts
Standard Deviation 0.05
|
0.4 micro volts
Standard Deviation 0.1
|
0.3 micro volts
Standard Deviation 0.1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline, five days post baselinePopulation: 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.
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.
Outcome measures
| Measure |
tACS (Alpha)
n=8 Participants
10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily
tACS (alpha)
|
tDCS
n=7 Participants
2mA stimulation for 20 minutes twice daily
tDCS
|
Sham Stimulation
n=7 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.
tACS (alpha)
|
|---|---|---|---|
|
Change in Electroencephalogram (EEG) Auditory Tasks: Click Train Task From Baseline
topographical activity
|
5 inter-trial phase coherence
Standard Deviation 0.1
|
0.5 inter-trial phase coherence
Standard Deviation 0.1
|
0.5 inter-trial phase coherence
Standard Deviation 0.1
|
|
Change in Electroencephalogram (EEG) Auditory Tasks: Click Train Task From Baseline
time-frequency activity
|
1 inter-trial phase coherence
Standard Deviation 0.01
|
0.05 inter-trial phase coherence
Standard Deviation 0.01
|
0.04 inter-trial phase coherence
Standard Deviation 0.01
|
Adverse Events
tACS (Alpha)
tDCS
Sham Stimulation
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Dr. Flavio Frohlich
University of North Carolina at Chapel Hill
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place