STimulation to Improve Auditory haLLucinations

Study Overview
=================
Brief Summary
-----------------
Investigating the effects of non-invasive transcranial current stimulation as a treatment for auditory hallucinations in patients with schizophrenia.

Detailed Description
-----------------
The investigator's primary objective is to conduct a pilot clinical trial to establish the feasibility and to collect first effectiveness data for the use of transcranial alternating current stimulation (tACS) to re-normalize pathological alpha oscillations in dorso-lateral prefrontal cortex (dl-PFC) of patients with schizophrenia or schizoaffective disorder by comparing Auditory Hallucination Rating Scale (AHRS) scores immediately before the first stimulation session and immediately after the last stimulation session. As a secondary objective the investigators will assess the differential clinical effects of sham, 10 Hz and 2 mA transcranial direct current stimulation (tDCS) on electroencephalogram (EEG) measures of alpha oscillations.

Official Title
-----------------
Targeting Auditory Hallucinations With Alternating Current Stimulation

Conditions
-----------------
Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
-----------------
* Device: tACS (alpha)
* Device: tDCS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: DSM-IV diagnosis of schizophrenia, any subtype, or schizoaffective disorder, with refractory auditory hallucinations. Duration of illness >1 year 18-70 years old Clinically stable for at least 12 weeks, i.e. not requiring hospitalization or a change in level of care On current antipsychotic doses for at least 4 weeks 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 informed consent on the patient's behalf with the patient providing written assent to participate. Exclusion Criteria: DSM-IV diagnosis of alcohol of 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 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 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 an adequate method of contraception during study participation for those of childbearing potential Positive urine test for cannabis, cocaine, amphetamine, barbiturates, benzodiazepines, opiates

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tACS (alpha)<br>20 participants: 10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily | Device: tACS (alpha)<br> <br> |
| Experimental: tDCS<br>20 participants: 2mA stimulation for 20 minutes twice daily | Device: tDCS<br> <br> |
| Sham Comparator: Sham stimulation<br>20 participants: Will include 10 seconds of ramp in to 1 minutes of 10 Hz tACS with a ramp out of 10 seconds for a total of 80 seconds of stimulation twice daily. | Device: tACS (alpha)<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportional Change From Baseline in Auditory Hallucination Rating Scale (AHRS) Score | The Auditory Hallucination Rating Scale (AHRS) measures the severity of auditory hallucinations in the past week. The scale assesses frequency, duration, location, loudness, belief of origin of voices, negative content, distress, disruption to life, and control over voices. All items are measured on a scale of 0 to 4, with a total possible score of 44. Higher scores indicate higher severity of auditory hallucinations. The investigators will compare the AHRS scores from immediately before the first stimulation and immediately after the last stimulation session as the investigator's primary outcomes measure. | Baseline, five days post baseline, 2 weeks post baseline, 5 weeks post baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alpha Oscillations Measured With Electroencephalogram (EEG) Resting State From Baseline | The investigators will compare alpha oscillation power from resting state EEG recordings on the first and last day of stimulation. The investigators will also collect EEG recordings data at the one week and one month follow up visits. The investigators will use each of the four EEG recordings as data to analyze alpha frequency activity as a pilot study for derivation of EEG biomarkers. | Baseline, five days post baseline | 
| Change in Positive and Negative Syndrome Scale (PANSS) Scores | The investigators will compare the PANSS total scores immediately before first stimulation session and immediately after last stimulation session as secondary outcome measures. Scores range from 30 to 210, with higher scores indicating more severe symptomology. | baseline, five days post baseline, five weeks post baseline | 
| Change in Brief Assessment of Cognition in Schizophrenia (BACS) Score | The Brief Assessment of Cognition in Schizophrenia (BACS) is a battery of cognitive assessments assessing verbal memory and learning, working memory, motor function, verbal fluency, speed of processing, and executive function. Higher scores indicate better cognitive performance. The investigators will compare the BACS total scores immediately before first stimulation session and immediately after last stimulation session as secondary outcome measures. Verbal Memory: Score out of 75 Digit Sequencing: Score out of 28 Token Motor: Score out of 100 Fluency: No score limit Symbol Coding: Score out of 110 Tower of London: Score out of 22 Reported score is the mean of these 6 subtests. Healthy controls (Keefe et al., 2006) scored 45.6 as a comparison. | baseline, five days post baseline, five weeks post baseline | 
| Change in Peak Frequency of Functional Connectivity From Baseline Measured With Electroencephalogram (EEG) Resting State | The investigators will compare peak frequency of functional connectivity from resting state EEG recordings on the first and last day of stimulation. The investigators will also collect EEG recordings data at the one week and one month follow up visits. The investigators will use each of the four EEG recordings as data to analyze the change in peak frequency of functional connectivity as a pilot study for derivation of EEG biomarkers. | Baseline, five days post baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
tACS, tDCS, sham, auditory hallucinations, Schizophrenia, Schizoaffective Disorder