STimulation to Improve Auditory haLLucinations (STILL 2)

Targeting Auditory Hallucinations With Alternating Current Stimulation

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

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder
• Intervention / Treatment: Device: tDCS; Device: tACS (alpha)

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tACS (alpha); 20 participants: 10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily	Device: tACS (alpha)
Experimental: tDCS; 20 participants: 2mA stimulation for 20 minutes twice daily	Device: tDCS
Sham Comparator: Sham stimulation; 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)

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Electroencephalogram (EEG) Auditory Tasks: Oddball Task From Baseline	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.	baseline, five days post baseline
Change in Electroencephalogram (EEG) Auditory Tasks: Click Train Task From Baseline	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.	baseline, five days post baseline

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institute of Mental Health (NIMH)

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: February 2, 2015
• First Submitted That Met QC Criteria: February 4, 2015
• First Posted (Estimate): February 10, 2015

Study Record Updates

• Last Update Posted (Actual): April 27, 2018
• Last Update Submitted That Met QC Criteria: April 15, 2018
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Schizophrenia; tDCS; Schizoaffective Disorder; tACS; auditory hallucinations; sham
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Schizophrenia Spectrum and Other Psychotic Disorders; Perceptual Disorders; Schizophrenia; Psychotic Disorders; Hallucinations
• Other Study ID Numbers: 14-3285; 1R21MH105574-01 (U.S. NIH Grant/Contract)