Effects of Transcranial Direct Current Stimulation (tDCS) on Persistent Auditory Verbal Hallucinations in Schizophrenia

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Primary Purpose

Status

Unknown status

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Transcranial direct current stimulation (tDCS)

About this trial

This is an interventional treatment trial for Auditory Hallucination, Verbal focused on measuring Schizophrenia, Transcranial direct current stimulation (tDCS), Schizoaffective disorder, EEG, Brain imaging, Cognition

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Patients - Inclusion Criteria:

Primary diagnosis of schizophrenia or schizoaffective disorder
Clinically stable (discretion of psychiatrist)
Consistent history of AVHs over the course of illness
>3 AVHs per week
Positive and Negative Syndrome Scale (PANSS) score of >3
Primary medications limited to one of the atypical antipsychotics (medications stabilized for 4 weeks prior to enrollment)

Patients - Exclusion Criteria:

Experiencing an acute psychotic episode
Current drug/alcohol dependence
Significant medical illness & mental retardation/learning disability
Extra-pyramidal symptoms resulting in disordered movement
Abnormal audiometric assessment (thresholds for pure tones >25 dB)
History of significant neurological issues & head injuries/concussions resulting in loss of consciousness for >5 minutes

Healthy Controls - Inclusion Criteria:

In good physical health
No history of serious mental health issues

Healthy Controls - Exclusion Criteria:

Personal history of psychiatric disorder
Family history of schizophrenia in first degree relatives & history of mental health issues in first degree relatives that required extensive treatment or hospitalization
Current/history of substance abuse
Significant medical illness
Extra-pyramidal symptoms resulting in movement disorder
Abnormal audiometric assessment (thresholds for pure tones >25 dB)
Significant neurological issues & head injuries/concussions resulting in loss of consciousness for >5 minutes

Sites / Locations

Royal Ottawa Mental Health CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Sham Comparator

Other

No Intervention

Arm Label

Active tDCS

Sham tDCS

Open-label Active tDCS

Healthy Control

Arm Description

Administration of a 2 milliamp (mA) current delivered via two scalp electrodes for 20 minutes (ramp-in + ramp-out periods, 30s total) 2 times per day for 5 consecutive days, >3 hour interval between sessions, for a total of 10 tDCS sessions. tDCS will be administered with a constant current regulator (NeuroConn DC-Stimulator Plus®, Germany) using 2 saline-soaked sponge electrodes applied over the scalp. Using the 10-20 international EEG system for tDCS electrode placement, the anode will be positioned midway between F3 and Fp1 (left DLPFC) and the cathode midway between T3 and P3 (left TPJ).

Administration of 2mA tDCS for 30 seconds followed by 19.5 minutes of no current via two scalp electrodes for 20 min (2X/day for 5 consecutive days) with >3 hours interval between sessions, for a total of 10 tDCS sessions.

Subjects who have received sham tDCS will be given the option to subsequently receive 10 sessions of open-label active tDCS (2X/day for 5 consecutive days) with >3 hours interval between sessions, for a total of 10 tDCS sessions.

Healthy volunteers will complete the same questionnaires, EEG recording procedures, and neuroimaging scans as the schizophrenia patient group, but will not undergo tDCS.

Outcomes

Primary Outcome Measures

Change in auditory hallucination severity measured by the Psychotic Symptom Rating Scale (PSYRATS)

The PSYRATS is a multidimensional measure of auditory hallucinations, including 11 items rated on five-point (0-4) scales (total score range 0-44). Symptoms are rated over the last week, with higher scores reflecting more severe symptoms. The dimensions assessed are frequency, duration, location, loudness, beliefs about origin, negative content, intensity of negative content, amount of distress, intensity of distress, disruption of life and control.

Secondary Outcome Measures

Change in Voice Power Differential Scale (VPDS) Scores

The Voice Power Differential Scale (VPDS) is a 7-item scale used to measure the perceived power differences between the voice and the voice hearer. Each item is rated on a five-point scale (1-5), with higher scores indicating greater power differential in favour of the voices, with total scores ranging from 7-35.

Change in Beliefs about Voices Questionnaire-Revised (BAVQ-R) Scores

The BAVQ-R is a 35-item questionnaire assessing people's beliefs about auditory hallucinations, and their emotional and behavioural reactions to them. All responses are rated on a 4-point scale: disagree (0); unsure (1); agree slightly (2); agree strongly (3), the measure thus assesses degree of endorsement of items. The scale consists of five subscales: malevolence (score range 0-18), benevolence (0-18), omnipotence (0-18), resistance (0-27), and engagement (0-24).

Change in Voices Acceptance and Action Scale (VAAS) Scores

The VAAS was developed to assess acceptance-based or action-based beliefs in response to auditory verbal hallucinations, in general and specifically to command hallucinations. This 31-item scale is divided into section A (i.e., 12 item stand-alone scale for general auditory hallucinations) and section B, referring specifically to command hallucinations. The participant is asked to rate their opinion from 1 'Strongly Disagree' to 5 'Strongly Agree', with higher scores meaning higher levels of acceptance and perception of acting according to one's valued life directions. Section A scores can range from 12-60, while section B scores can range from 19-95.

Change in Electroencephalography (EEG) - Resting-State Alpha Power

Changes in resting-state EEG power in alpha band. Resting-state recordings completed in both eyes-closed and eyes-open conditions, 5 minutes each.

Change in Electroencephalography (EEG) - Resting-State Beta Power

Changes in resting-state EEG power in beta band. Resting-state recordings completed in both eyes-closed and eyes-open conditions, 5 minutes each.

Change in Electroencephalography (EEG) - Resting-State Delta Power

Changes in resting-state EEG power in delta band. Resting-state recordings completed in both eyes-closed and eyes-open conditions, 5 minutes each.

Change in Electroencephalography (EEG) - Resting-State Theta Power

Changes in resting-state EEG power in theta band. Resting-state recordings completed in both eyes-closed and eyes-open conditions, 5 minutes each.

Change in Electroencephalography (EEG) - Resting-State Gamma Power

Changes in resting-state EEG power in gamma band. Resting-state recordings completed in both eyes-closed and eyes-open conditions, 5 minutes each.

Change in Electroencephalography (EEG) - Mismatch Negativity (MMN)

Change in MMN peak amplitudes and latencies to non-speech (tonal) deviants and speech (syllabic) deviants during the multi-feature optimal MMN paradigm.

Change in Electroencephalography (EEG) - P50

Change in T/C ratio (testing stimulus/conditioning stimulus) during paired click test. Change in T/C difference (testing stimulus - conditioning stimulus) during paired click test

Change in Brain Functional Magnetic Resonance Imaging (fMRI) - Resting-State

Changes in resting-state activity and connectivity within and between the auditory cortex and select regions of the default-mode network.

Change in Brain Functional Magnetic Resonance Imaging (fMRI) - Mismatch Negativity (tonal)

Changes in task-related activity and connectivity within and between the auditory cortex and select regions of the default-mode network .

Change in Brain Magnetic Resonance Spectroscopy (MRS)

Changes in glutamate/glutamine (Glu/Gln) concentrations in the auditory cortex.

Change in Cambridge Neuropsychological Test Automated Battery (CANTAB) Schizophrenia Battery

Changes in cognitive functioning abilities in core domains often affected in psychosis.

Change in Social Cognition - Social Attribution Task

Changes in social cognition/social inference abilities measured by a computerized social attribution task.

Full Information

NCT ID

NCT04222582

First Posted

April 15, 2019

Last Updated

January 6, 2020

Sponsor

University of Ottawa

Collaborators

The Royal Ottawa Mental Health Centre

1. Study Identification

Unique Protocol Identification Number

NCT04222582

Brief Title

Effects of Transcranial Direct Current Stimulation (tDCS) on Persistent Auditory Verbal Hallucinations in Schizophrenia

Official Title

The Neural, Behavioural, and Cognitive Outcomes of Transcranial Direct Current Stimulation (tDCS) for Persistent Auditory Verbal Hallucinations in Schizophrenia

Study Type

Interventional

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Unknown status

Study Start Date

January 1, 2019 (Actual)

Primary Completion Date

January 2021 (Anticipated)

Study Completion Date

January 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Ottawa

Collaborators

The Royal Ottawa Mental Health Centre

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

5. Study Description

Brief Summary

Many individuals with schizophrenia struggle with auditory verbal hallucinations (AVHs). In some cases, these AVHs can be resistant to medication treatment. Previous research has found that transcranial direct current stimulation (tDCS) can be helpful in treating symptoms in individuals with other psychiatric disorders, such as depression. This study will assess if tDCS is effective in treating AVHs in individuals with schizophrenia. tDCS is a non-invasive form of brain stimulation which uses a weak current to temporarily excite or inhibit underlying cortical regions with small electrodes placed on the scalp. tDCS has been found to improve mental processes, including attention and memory function. In addition to examining the effect of tDCS on AVHs, this study will assess the effects of tDCS on mood as well as brain electrical activity with electroencephalogram (EEG) recordings. As an additional component, participants will be invited to participate in neuroimaging. Using magnetic resonance imaging (MRI), brain activity and structure will be examined before and after tDCS. tDCS will be administered twice daily for 5 consecutive days for a total of 10 sessions. These study findings will contribute to the understanding of the impact of tDCS on AVHs, and will also increase knowledge of sound and memory/cognitive processing in individuals with schizophrenia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Auditory Hallucination, Verbal

Keywords

Schizophrenia, Transcranial direct current stimulation (tDCS), Schizoaffective disorder, EEG, Brain imaging, Cognition

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

84 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Active tDCS

Arm Type

Active Comparator

Arm Description

Administration of a 2 milliamp (mA) current delivered via two scalp electrodes for 20 minutes (ramp-in + ramp-out periods, 30s total) 2 times per day for 5 consecutive days, >3 hour interval between sessions, for a total of 10 tDCS sessions. tDCS will be administered with a constant current regulator (NeuroConn DC-Stimulator Plus®, Germany) using 2 saline-soaked sponge electrodes applied over the scalp. Using the 10-20 international EEG system for tDCS electrode placement, the anode will be positioned midway between F3 and Fp1 (left DLPFC) and the cathode midway between T3 and P3 (left TPJ).

Arm Title

Sham tDCS

Arm Type

Sham Comparator

Arm Description

Administration of 2mA tDCS for 30 seconds followed by 19.5 minutes of no current via two scalp electrodes for 20 min (2X/day for 5 consecutive days) with >3 hours interval between sessions, for a total of 10 tDCS sessions.

Arm Title

Open-label Active tDCS

Arm Type

Other

Arm Description

Subjects who have received sham tDCS will be given the option to subsequently receive 10 sessions of open-label active tDCS (2X/day for 5 consecutive days) with >3 hours interval between sessions, for a total of 10 tDCS sessions.

Arm Title

Healthy Control

Arm Type

No Intervention

Arm Description

Healthy volunteers will complete the same questionnaires, EEG recording procedures, and neuroimaging scans as the schizophrenia patient group, but will not undergo tDCS.

Intervention Type

Device

Intervention Name(s)

Transcranial direct current stimulation (tDCS)

Intervention Description

Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which uses a weak current (2mA direct current) to temporarily excite or inhibit underlying brain regions with small electrodes placed on the scalp.

Primary Outcome Measure Information:

Title

Change in auditory hallucination severity measured by the Psychotic Symptom Rating Scale (PSYRATS)

Description

The PSYRATS is a multidimensional measure of auditory hallucinations, including 11 items rated on five-point (0-4) scales (total score range 0-44). Symptoms are rated over the last week, with higher scores reflecting more severe symptoms. The dimensions assessed are frequency, duration, location, loudness, beliefs about origin, negative content, intensity of negative content, amount of distress, intensity of distress, disruption of life and control.

Time Frame

Baseline, after 2nd tDCS session on days 1, 3, and 5, and follow-up (within a week of completing tDCS)

Secondary Outcome Measure Information:

Title

Change in Voice Power Differential Scale (VPDS) Scores

Description

The Voice Power Differential Scale (VPDS) is a 7-item scale used to measure the perceived power differences between the voice and the voice hearer. Each item is rated on a five-point scale (1-5), with higher scores indicating greater power differential in favour of the voices, with total scores ranging from 7-35.

Time Frame