Targeting Auditory Hallucinations With Alternating Current Stimulation

Not Applicable

Completed

Conditions: Schizophrenia
Schizo Affective Disorder

Interventions: Device: tACS treatment week
Device: tACS sham week
Device: Maintenance tACS
Device: Maintenance Sham tACS

Registration Number: NCT03221270

Lead Sponsor: University of North Carolina, Chapel Hill

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 25

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
tACS Treatment & tACS Maintenance	tACS treatment week	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 & tACS Maintenance	Maintenance tACS	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.
Sham tACS Treatment & Sham tACS Maintenance	Maintenance Sham tACS	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.
Sham tACS Treatment & Sham tACS Maintenance	tACS sham week	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.
Sham tACS Treatment & tACS Maintenance	Maintenance tACS	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.
tACS Treatment & Sham tACS Maintenance	Maintenance Sham tACS	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 & Sham tACS Maintenance	tACS treatment week	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.
Sham tACS Treatment & tACS Maintenance	tACS sham week	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.