Targeting Auditory Hallucinations With Alternating Current Stimulation (STILL3)

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

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizo Affective Disorder
• Intervention / Treatment: Device: tACS treatment week; Device: Maintenance tACS; Device: tACS sham week; Device: Maintenance Sham tACS

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 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 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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / 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: Neuroconn DC Stimulator; 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: Neuroconn DC Stimulator
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: Neuroconn DC Stimulator; 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: Neuroconn DC Stimulator
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: 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: Neuroconn DC Stimulator; 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: Neuroconn DC Stimulator
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: Neuroconn DC Stimulator; 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: Neuroconn DC Stimulator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Auditory Hallucination Rating Scale (AHRS) Score	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.	Baseline, immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Signal Change in the Average Alpha Oscillation Power From Eyes-Open Resting State Electroencephalogram (EEG)	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.	Change from baseline to immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation.
Average Score on the Positive and Negative Syndrome Scales (PANSS)	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.	Baseline, immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation.
Brief Assessment Cognition in Schizophrenia (BACS)	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.	Baseline, immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electroencephalogram (EEG) Auditory Task	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.	Change across time from baseline measurement to final maintenance stimulation
Auditory Hallucination Rating Scale (AHRS)	The investigators will compare the AHRS scores from baseline across the 8 weeks of maintenance stimulation sessions as an outcome measure.	Change from Baseline AHRS at final maintenance stimulation session.
Positive and Negative Syndrome Scale (PANSS)	The investigators will compare the PANSS scores from baseline across the 8 weeks of maintenance stimulation sessions as an outcome measure.	Change from Baseline PANSS at final maintenance stimulation session.
Brief Assessment Cognition in Schizophrenia (BACS)	The investigators will compare the BACS scores from baseline across the 8 weeks of maintenance stimulation sessions as an outcome measure.	Change from Baseline BACS at final maintenance stimulation session.

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.
• Frohlich 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 14, 2017
• Primary Completion (ACTUAL): January 5, 2021
• Study Completion (ACTUAL): January 5, 2021

Study Registration Dates

• First Submitted: July 14, 2017
• First Submitted That Met QC Criteria: July 17, 2017
• First Posted (ACTUAL): July 18, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 16, 2022
• Last Update Submitted That Met QC Criteria: February 15, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Schizophrenia; EEG; tACS; Sham; Auditory Hallucinations; Schizo Affective Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Schizophrenia Spectrum and Other Psychotic Disorders; Perceptual Disorders; Schizophrenia; Psychotic Disorders; Mood Disorders; Hallucinations
• Other Study ID Numbers: 17-1364; 4R33MH105574-03 (NIH)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes