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STimulation to Improve Auditory haLLucinations (STILL 2)

Primary Purpose

Schizophrenia, Schizoaffective Disorder

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
tACS (alpha)
tDCS
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, tDCS, sham, auditory hallucinations, Schizophrenia, Schizoaffective Disorder

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 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

Sites / Locations

  • UNC Chapel Hill

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Sham Comparator

Arm Label

tACS (alpha)

tDCS

Sham stimulation

Arm Description

20 participants: 10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily

20 participants: 2mA stimulation for 20 minutes twice daily

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
February 2, 2015
Last Updated
April 15, 2018
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
NCT02360228
Brief Title
STimulation to Improve Auditory haLLucinations
Acronym
STILL 2
Official Title
Targeting Auditory Hallucinations With Alternating Current Stimulation
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
May 2015 (undefined)
Primary Completion Date
February 2017 (Actual)
Study Completion Date
February 2017 (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

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizoaffective Disorder
Keywords
tACS, tDCS, sham, auditory hallucinations, Schizophrenia, Schizoaffective Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
tACS (alpha)
Arm Type
Experimental
Arm Description
20 participants: 10Hz tACS with a peak-to-peak amplitude of 2mA for 20 minutes twice daily
Arm Title
tDCS
Arm Type
Experimental
Arm Description
20 participants: 2mA stimulation for 20 minutes twice daily
Arm Title
Sham stimulation
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
tACS (alpha)
Intervention Type
Device
Intervention Name(s)
tDCS
Primary Outcome Measure Information:
Title
Proportional Change From Baseline in 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 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.
Time Frame
Baseline, five days post baseline, 2 weeks post baseline, 5 weeks post baseline
Secondary Outcome Measure Information:
Title
Change in Alpha Oscillations Measured With Electroencephalogram (EEG) Resting State From Baseline
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 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.
Time Frame
Baseline, five days post baseline
Title
Change in Positive and Negative Syndrome Scale (PANSS) Scores
Description
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.
Time Frame
baseline, five days post baseline, five weeks post baseline
Title
Change in Brief Assessment of Cognition in Schizophrenia (BACS) Score
Description
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.
Time Frame
baseline, five days post baseline, five weeks post baseline
Title
Change in Peak Frequency of Functional Connectivity From Baseline Measured With Electroencephalogram (EEG) Resting State
Description
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.
Time Frame
Baseline, five days post baseline
Other Pre-specified Outcome Measures:
Title
Change in Electroencephalogram (EEG) Auditory Tasks: Oddball Task From Baseline
Description
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.
Time Frame
baseline, five days post baseline
Title
Change in Electroencephalogram (EEG) Auditory Tasks: Click Train Task From Baseline
Description
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.
Time Frame
baseline, five days post baseline

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 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
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.
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STimulation to Improve Auditory haLLucinations

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