Transcranial Brain Stimulation and Its Underlying Neural Mechanisms as a Novel Treatment for Auditory Hallucinations

The present study aims to investigate whether transcranial direct current stimulation (tDCS) reduces auditory hallucinations in patients with psychosis. In addition, the neuronal changes of tDCS will be examined.

Study Overview

• Status: Completed
• Conditions: Psychotic Disorders
• Intervention / Treatment: Device: DC Stimulator PLUS (NeuroConn)

Detailed Description

The majority of patients with psychosis experience hallucinations, particularly auditory hallucinations are frequent. The hallucinations often leads to massive distress and impairments in social functioning and sometimes even order patients to commit acts of violence against themselves or others. The standard treatment for auditory hallucinations is antipsychotic medication. However, side-effects can be severe and about 25-30% of the patients do not respond to the medication. Transcranial direct current stimulation is a non-invasive brain stimulation technique, which modulates cortical excitability in a pain-free free with mild transient adverse effects, if any. Typically, cortical excitability underneath the anode is boosted while cathodal stimulation has inhibitory effects. Previous studies found that 2 daily sessions of 20 min tDCS for five subsequent days may reduce auditory hallucinations. Investigators want to further assess the efficacy of tDCS in sample that is large enough to detect medium to large effects. In addition, investigators want to investigate the neural mechanisms that underlie the tDCS treatment by examining various neuroimaging parameters before, immediately after treatment, and 3 months after treatment.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Hordaland
    • Bergen, Hordaland, Norway, 5009
      • University of Bergen

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosed with schizophrenia spectrum disorder or other psychotic disorder
• Frequent auditory hallucinations (at least 5 times a week).
• Patients are on a stable dose of antipsychotic medication (which can also be zero) for at least 2 weeks.
• Mentally competent for informed consent.
• Provided informed consent.

Exclusion Criteria:

• Metal objects in or around the head that cannot be removed (i.e. cochlear implant, surgical clips, piercing)
• History of seizures, or a history of seizures in first-degree relatives.
• History of eye trauma with a metal object or professional metal workers
• History of brain surgery, brain infarction, head trauma, cerebrovascular accident, broken skull, brain tumour, heart disease, cardiac pacemaker.
• Skin disease on the scalp on the position of the tDCS electrodes
• Coercive treatment based on a judicial ruling
• Pregnancy in female patients

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: real tDCS; DC Stimulator PLUS (NeuroConn) The real tDCS condition comprises two daily sessions of 20 min tDCS, separated by a minimum break of 3h, for five consecutive days. Anodal and cathodal tDCS will be applied with 2mA to the left dorsolateral prefrontal cortex (a point midway between F3 and FP1) and the left peri-Sylvian region (a point midway between T3 and P3), respectively. Electrode size is 7cm x 5cm.	Device: DC Stimulator PLUS (NeuroConn)
Sham Comparator: sham tDCS; DC Stimulator PLUS (NeuroConn) The sham condition is identical to the "real tDCS" condition except that after 40s of tDCS stimulation is going to be reduced to a small pulse every 550msec (110 μA over 15 msec) through the remainder of the 20 minute period.	Device: DC Stimulator PLUS (NeuroConn)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Auditory Hallucination Rating Scale (AHRS)	Measure for severity of hallucinations	Change from Baseline to immediately after treatment and 3 months after treatment
Questionnaire for Psychotic Experiences (QPE)	Measure for severity of hallucinations	Change from Baseline to immediately after treatment and 3 months after treatment
Positive and Negative Syndrome Scale (PANSS)	Measure for positive and negative symptoms in psychotic disorders	Change from Baseline to immediately after treatment and 3 months after treatment
Hallucinations App	iPhone/iPod application for self-ratings of auditory hallucinations	Continuously between baseline and 3 months after treatment
Hallucination Change Scale (HCS)	Measure for changes in severity of auditory hallucinations	Change from Baseline to immediately after treatment and 3 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stroop task	Measure of executive functioning	Change from Baseline to immediately after treatment and 3 months after treatment
Trailmaking test A and B	Measure of visuomotor speed	Change from Baseline to immediately after treatment and 3 months after treatment
Expectations Questionnaire	prior expectations participants have regarding the outcome of the treatment on a scale from 0 ("The treatment will have no effect") to 10 ("The treatment will make the voices go away entirely.")	Change from Baseline to immediately after treatment and 3 months after treatment
Adverse Effects Questionnaire	The presence and severity of side-effects will be monitored using the tDCS adverse effects questionnaire	The questionnaire is completed after each tDCS session. That is, twice on each day of the five day treatment program
The Clinical Global Impressions Scale - Severity	Measure of global functioning	Change from Baseline to immediately after treatment and 3 months after treatment
Global Assessment of Functioning	Measure of global functioning	Change from Baseline to immediately after treatment and 3 months after treatment
Shape, size, and integrity of gray and white matter structures in the brain	Structural Magnetic Resonance Imaging (MRI)	Change from Baseline to immediately after treatment and 3 months after treatment
GABA and glutamate levels in the dorsolateral prefrontal cortex and peri-Sylvian regions	MR spectroscopy	Change from Baseline to immediately after treatment and 3 months after treatment
BOLD (Blood Oxygenation Level Dependent signal) response during resting state	Resting state functional MRI	Change from Baseline to immediately after treatment and 3 months after treatment
Dichotic listening paradigm	Measure of executive functioning	Change from Baseline to immediately after treatment and 3 months after treatment
Dichotic listening paradigm	Measure of language lateralization	Change from Baseline to immediately after treatment and 3 months after treatment
BOLD response during dichotic listening paradigm	Changes in brain activity in the left dorsolateral prefrontal cortex and the peri-Sylvian language regions	Change from Baseline to immediately after treatment and 3 months after treatment
White matter structure and connectivity	MR Diffusion Tensor Imaging	Change from Baseline to immediately after treatment and 3 months after treatment

Collaborators and Investigators

• Sponsor: University of Bergen
• Collaborators: Helse-Bergen HF
• Investigators: Principal Investigator: Marco Hirnstein, PhD, University of Bergen

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: May 6, 2016
• First Submitted That Met QC Criteria: May 9, 2016
• First Posted (Estimate): May 11, 2016

Study Record Updates

• Last Update Posted (Actual): August 7, 2020
• Last Update Submitted That Met QC Criteria: August 6, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Schizophrenia Spectrum and Other Psychotic Disorders; Perceptual Disorders; Psychotic Disorders; Mental Disorders; Hallucinations
• Other Study ID Numbers: UiB-BFS-01/2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared with the ERC Advanced Projects Advanced Grant #249516 "VOICE" and #693124 "ONOFF".