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Targeting Auditory Hallucinations With Alternating Current Stimulation (STILL3)

Primary Purpose

Schizophrenia, Schizo Affective Disorder

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
tACS treatment week
tACS sham week
Maintenance tACS
Maintenance Sham tACS
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring tACS, Sham, Auditory Hallucinations, Schizophrenia, Schizo Affective Disorder, EEG

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UNC Chapel Hill

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Sham Comparator

Other

Other

Arm Label

tACS Treatment & tACS Maintenance

Sham tACS Treatment & Sham tACS Maintenance

Sham tACS Treatment & tACS Maintenance

tACS Treatment & Sham tACS Maintenance

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
July 14, 2017
Last Updated
February 15, 2022
Sponsor
University of North Carolina, Chapel Hill
Collaborators
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT03221270
Brief Title
Targeting Auditory Hallucinations With Alternating Current Stimulation
Acronym
STILL3
Official Title
Targeting Auditory Hallucinations With Alternating Current Stimulation
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
November 14, 2017 (Actual)
Primary Completion Date
January 5, 2021 (Actual)
Study Completion Date
January 5, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizo Affective Disorder
Keywords
tACS, Sham, Auditory Hallucinations, Schizophrenia, Schizo Affective Disorder, EEG

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Model Description
Participants will initially be randomized to either sham or 10 Hz tACS for the 5 consecutive days of stimulation. Participants will then be re-randomized to either sham or 10 Hz tACS for the 8 weeks of maintenance stimulation.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
This is a double blind, randomized clinical trial.
Allocation
Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
tACS Treatment & tACS Maintenance
Arm Type
Experimental
Arm Description
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.
Arm Title
Sham tACS Treatment & Sham tACS Maintenance
Arm Type
Sham Comparator
Arm Description
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.
Arm Title
Sham tACS Treatment & tACS Maintenance
Arm Type
Other
Arm Description
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.
Arm Title
tACS Treatment & Sham tACS Maintenance
Arm Type
Other
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
tACS treatment week
Other Intervention Name(s)
Neuroconn DC Stimulator
Intervention Description
10 Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 20 minutes twice for 5 consecutive days.
Intervention Type
Device
Intervention Name(s)
tACS sham week
Other Intervention Name(s)
Neuroconn DC Stimulator
Intervention Description
10Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 10 seconds twice a day for 5 consecutive days.
Intervention Type
Device
Intervention Name(s)
Maintenance tACS
Other Intervention Name(s)
Neuroconn DC Stimulator
Intervention Description
10 Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 40 minutes once a weekly for 8 weeks.
Intervention Type
Device
Intervention Name(s)
Maintenance Sham tACS
Other Intervention Name(s)
Neuroconn DC Stimulator
Intervention Description
10Hz sine wave stimulation with a peak-to-peak amplitude of 2 mA for 10 seconds once a week for 8 weeks.
Primary Outcome Measure Information:
Title
Mean Auditory Hallucination Rating Scale (AHRS) Score
Description
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.
Time Frame
Baseline, immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation.
Secondary Outcome Measure Information:
Title
Percentage of Signal Change in the Average Alpha Oscillation Power From Eyes-Open Resting State Electroencephalogram (EEG)
Description
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.
Time Frame
Change from baseline to immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation.
Title
Average Score on the Positive and Negative Syndrome Scales (PANSS)
Description
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.
Time Frame
Baseline, immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation.
Title
Brief Assessment Cognition in Schizophrenia (BACS)
Description
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.
Time Frame
Baseline, immediately after five days of stimulation, and immediately after the 8th week of maintenance stimulation.
Other Pre-specified Outcome Measures:
Title
Electroencephalogram (EEG) Auditory Task
Description
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.
Time Frame
Change across time from baseline measurement to final maintenance stimulation
Title
Auditory Hallucination Rating Scale (AHRS)
Description
The investigators will compare the AHRS scores from baseline across the 8 weeks of maintenance stimulation sessions as an outcome measure.
Time Frame
Change from Baseline AHRS at final maintenance stimulation session.
Title
Positive and Negative Syndrome Scale (PANSS)
Description
The investigators will compare the PANSS scores from baseline across the 8 weeks of maintenance stimulation sessions as an outcome measure.
Time Frame
Change from Baseline PANSS at final maintenance stimulation session.
Title
Brief Assessment Cognition in Schizophrenia (BACS)
Description
The investigators will compare the BACS scores from baseline across the 8 weeks of maintenance stimulation sessions as an outcome measure.
Time Frame
Change from Baseline BACS at final maintenance stimulation session.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Flavio Frohlich, PhD
Organizational Affiliation
University of North Carolina at Chapel Hill - Department of Psychiatry
Official's Role
Principal Investigator
Facility Information:
Facility Name
UNC Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22581236
Citation
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.
Results Reference
background
PubMed Identifier
26866874
Citation
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.
Results Reference
background

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Targeting Auditory Hallucinations With Alternating Current Stimulation

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