SchizophreniaNCT03388554
The Effects of tDCS on Auditory Hallucination, Insight, Neurocognitive Function and HRV in Patients With Schizophrenia
A study testing tDCS in people with Schizophrenia and Schizoaffective Disorder, run by Tri-Service General Hospital (TSGH) at 1 site in Taiwan.
Trial summary
The study aimed to investigate whether transcranial direct current stimulation could modify auditory hallucination, insight, neurocognitive function, heart rate variability, psychosocial functioning and quality of life in patients with schizophrenia. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder, Auditory Hallucination, Verbal
- What is being tested?
- tDCS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteTaiwan
- Study dates
- Jul 2016to 2 Mar 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder were included in the study. All these patients showed refractory auditory verbal hallucinations,which are defined as the persistence of daily auditory verbal hallucinations without remission in spite of antipsychotic medications at an adequate dosage for at least 3 months.
Who cannot join
- Pregnancy or breastfeeding.
- Having epilepsy, severe physical illness, any current psychiatric comorbidity or history of substance dependence.
- Having contraindications for transcranial electrical/magnetic stimulation.
- Having intracranial metal foreign bodies.
- Having a history of intracranial neoplasms or surgery, or a history of severe head injuries or cerebrovascular diseases.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: To Investigate the Effects of Transcranial Direct Current Stimulation on Auditory Hallucination, Insight, Neurocognitive Function, Heart Rate Variability, Psychosocial Functioning and Quality of Life in Patients With Schizophrenia
The study aimed to investigate whether transcranial direct current stimulation could modify auditory hallucination, insight, neurocognitive function, heart rate variability, psychosocial functioning and quality of life in patients with schizophrenia.
Read the detailed description
Transcranial direct current stimulation (tDCS), a novel, non-invasive and safe neuro-modulating technique, has been developed as a new therapeutic option for neuropsychiatric disorders. It encompasses the induction of a relatively weak constant current flow through the cerebral cortex via scalp electrodes. Dependent on stimulation polarity, this results in a modulation of cortical excitability and spontaneous neural activity. The technique was established in the 1950s and 1960s primarily in animals. In these early studies it was shown that subthreshold DC stimulation increases spontaneous neuronal activity if the anode is placed above or within the cortex, while exposure to cathodal polarity results in reduced activity. This is caused by a subthreshold membrane depolarization by anodal and a hyperpolarization by cathodal stimulation. It was demonstrated in humans that the after-effects of tDCS depend on modifications of NMDA receptor-efficacy. The after-effects of tDCS are blocked by the NMDA receptor antagonist dextromethorphan, and prolonged by the partial NMDA receptor-agonist D-cycloserine. This tDCS polarity-dependent alteration of NMDA receptor function seems to be initiated by the respective membrane potential shift and probably by the accompanying cortical activity modification,because it is prevented by the sodium channel blocker carbamazepine. Intraneuronal calcium concentration also contributes, because calcium channel antagonists eliminate the excitability-enhancing aftereffects of anodal tDCS. Recently, tDCS has been found to improve psychopathological symptoms (auditory hallucination in particular), cognitive deficits and insight of schizophrenia and also strengthen cardiac autonomic function in healthy subjects. Further replication studies are needed.
The study aimed to investigate whether transcranial direct current stimulation could modify auditory hallucination, insight, neurocognitive function, heart rate variability, psychosocial functioning and quality of life in patients with schizophrenia.
Study design: randomized double-blind, sham-controlled study design.
Participants: 60 patients having a diagnosis of schizophrenia or schizoaffective with refractory auditory verbal hallucinations (defined as the persistence of daily auditory verbal hallucinations without remission in spite of antipsychotic medications at an adequate dosage for at least 3 months), aged 20-65 years.
Others: see Arms and Interventions, Eligibility Criteria or Outcome Measures.
- Conditions
- Schizophrenia, Schizoaffective Disorder, Auditory Hallucination, Verbal, Neurocognitive Dysfunction, Autonomic Imbalance, Psychosocial Impairment
- Being tested
- tDCS
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Hallucinations, Cognition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tDCSDevice
| Study group | Role | What they receive |
|---|---|---|
| Active tDCS | Active comparator | Direct current (DC) generated by a DC stimulator (Eldith DC stimulator: www. neuroconn.de/dc-stimulator_plus_en/) was bilaterally delivered through a pair of saline-soaked surface sponge electrodes (35 square centimeter). The anode was placed with the middle of the electrode over a point midway between F3 and FP1 (left dorsolateral prefrontal cortex and left prefrontal cortex). The cathode was located over a point midway between T3 and P3 (left temporo-parietal junction). Stimulation was applied at an intensity of 2 mA for 20 min, twice-daily on 5 consecutive weekdays. The twice daily sessions were separated by at least 3 hours. All patients in the active tDCS group were maintained on their antipsychotic medications throughout the study period. Receives: Device: tDCS |
| Sham tDCS | Sham comparator | In sham stimulation, the current was turned on for 30 sec and then ramped down to 0 mA. All patients in the sham tDCS group were maintained on their antipsychotic medications throughout the study period. Receives: Device: tDCS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes from baseline scores of Auditory Hallucination Rating Scale (AHRS) at the timepoint immediately after tDCS, at one month and three months after tDCS.
A clinician-administered rating scale to measure the severity of auditory (verbal) hallucination of the patients with schizophrenia spectrum disorder.
Measured: Three months.
Secondary outcomes (14)
Changes from baseline scores of Positive and Negative Syndrome Scale (PANSS) at the timepoint immediately after tDCS, at one month and three months after tDCS.
A clinician-administered rating scale to measure the severity of psychopathological symptoms of the patients with schizophrenia spectrum disorder.
Measured: Three months.
Changes from baseline scores at Personal and Social Performance scale (PSP) at the timepoint immediately after tDCS, at one month and three months after tDCS.
A clinician-administered rating scale to measure the psychosocial functioning of the patients with schizophrenia spectrum disorder.
Measured: Three months.
Changes from baseline results of Digit span (forward and backward)
A test to measure the capacity of working memory of the patients.
Measured: One month.
Changes from baseline results of Finger tapping test
A neuropsychological test that examines motor functioning, specifically, motor speed and lateralized coordination.
Measured: One month.
Changes from baseline results of Continuous Performance (CPT, version 2.0)
A neuropsychological test that examines the performance of prefrontal-mediated task.
Measured: One month.
Changes from baseline results of Wisconsin Card Sorting Test (WCST) at the timepoint immediately after tDCS and at one month after tDCS.
A neuropsychological test of "set-shifting", i.e. the ability to display flexibility in the face of changing schedules of reinforcement.
Measured: One month.
Changes from baseline results of Trail Making Test (TMT) at the timepoint immediately after tDCS and at one month after tDCS.
A neuropsychological test of visual attention and task switching.
Measured: One month.
Changes from baseline results of Tower of London test at the timepoint immediately after tDCS and at one month after tDCS.
A neuropsychological test for the assessment of executive functioning specifically to detect deficits in planning, which may occur due to a variety of medical and neuropsychiatric conditions.
Measured: One month.
Changes from baseline heart rate variability (HRV) at the timepoint immediately after tDCS and at one month after tDCS.
An index of autonomic functioning.
Measured: One month.
Changes from baseline scores of the brief version of questionnaire of The World Health Organization Quality of Life (WHOQOL-BREF Taiwan version) at the timepoint immediately after tDCS and at one month after tDCS.
A self-reported questionnaire to measure quality of life of the patients.
Measured: One month.
Changes from baseline scores of self-reported version of the graphic Personal and Social Performance scale (SRG-PSP) at the timepoint immediately after tDCS and at one month after tDCS.
A self-reported graphic questionnaire to measure psychosocial functioning of the patients.
Measured: One month.
Changes from baseline scores of the abbreviated version of the Scale to Assess Unawareness in Mental Disorder in schizophrenia (SUMD) at the timepoint immediately after tDCS, at one month and three months after tDCS.
An expert-rating scale based on a patient interview to measure the insight of the patient.
Measured: Three months.
Changes from baseline scores of the Taiwanese version of the Beck Cognitive Insight Scale (BCIS) at the timepoint immediately after tDCS and at one month after tDCS.
Translated BCIS has two subscales including reflective attitude (R, 9 items, score range 9-36) and certain attitude (C, 6 items, score range 6-24) subscales. The higher score in R subscale indicates higher self-reflectiveness while the higher score in C subscale indicates higher self-certainty. Thus, a composite index (R-C, reflective attitude minus certain attitude, score range 3-30) of the translated BCIS represents the measurement of cogntive insight . The higher score of R-C index indicates higher cognitive insight.
Measured: One month.
Changes from baseline scores of the Taiwanese version of the Self- Appraisal of Illness Questionnaire (SAIQ) at the timepoint immediately after tDCS and at one month after tDCS.
This scale is a self-report instrument composed of 17 items on which participants are asked to rate the extent to which they agree with each statement using a four-point Likert scale, ranging from 0, ''do not agree at all'', to 3, ''agree completely'', which varies according to the statement or questions content. SAIQ has three subscales including worry, need for treatment, and presence/outcome of illness subscales. The scores for the three subscales were summed to create a total SAIQ score (range 17-68), which is intended to represent a broad measure of insight. Lower SAIQ total scores indicate less awareness of one's psychiatric illness.
Measured: One month.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2018
- Study startJul 2016
- Primary completion2 Mar 2018
- Study completion2 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Direct current (DC) generated by a DC stimulator (Eldith DC stimulator: www. neuroconn.de/dc-stimulator\_plus\_en/) was bilaterally delivered through a pair of saline-soaked surface sponge electrodes (35 square centimeter). The anode was placed with the middle of the electrode over a point midway between F3 and FP1 (left dorsolateral prefrontal cortex and left prefrontal cortex). The cathode was located over a point midway between T3 and P3 (left temporo-parietal junction). Stimulation was applied at an intensity of 2 mA for 20 min, twice-daily on 5 consecutive weekdays. The twice daily sessions were separated by at least 3 hours.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tri-Service General Hospital (TSGH)
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hsin-An Chang, MD, Tri-Service General Hospital (TSGH)
- Investigators
- Hsin-An Chang, M.D., Principal investigator, Tri-Service General Hospital, National Defense Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03388554
- Sponsor's protocol ID
- 2-103-03-002-2
- Status last verified
- Apr 2018
- First submitted
- 24 Dec 2017
- Last updated
- 1 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- To Investigate the Effects of Transcranial Direct Current Stimulation on Auditory Hallucination, Insight, Neurocognitive Function, Heart Rate Variability, Psychosocial Functioning and Quality of Life in Patients With Schizophrenia
- ClinicalTrials.gov ID
- NCT03388554
- Acronym / sponsor ID
- 2-103-03-002-2
- Conditions
- Schizophrenia, Schizoaffective Disorder, Auditory Hallucination, Verbal, Neurocognitive Dysfunction, Autonomic Imbalance, Psychosocial Impairment
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Tri-Service General Hospital (TSGH)University, hospital or other
- Study start
- Jul 2016 (actual)
- Primary completion
- 2 Mar 2018 (actual)
- Study completion
- 2 Mar 2018 (actual)
- First posted
- 3 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study aimed to investigate whether transcranial direct current stimulation could modify auditory hallucination, insight, neurocognitive function, heart rate variability, psychosocial functioning and quality of life in patients with schizophrenia.
Detailed description
Transcranial direct current stimulation (tDCS), a novel, non-invasive and safe neuro-modulating technique, has been developed as a new therapeutic option for neuropsychiatric disorders. It encompasses the induction of a relatively weak constant current flow through the cerebral cortex via scalp electrodes. Dependent on stimulation polarity, this results in a modulation of cortical excitability and spontaneous neural activity. The technique was established in the 1950s and 1960s primarily in animals. In these early studies it was shown that subthreshold DC stimulation increases spontaneous neuronal activity if the anode is placed above or within the cortex, while exposure to cathodal polarity results in reduced activity. This is caused by a subthreshold membrane depolarization by anodal and a hyperpolarization by cathodal stimulation. It was demonstrated in humans that the after-effects of tDCS depend on modifications of NMDA receptor-efficacy. The after-effects of tDCS are blocked by the NMDA receptor antagonist dextromethorphan, and prolonged by the partial NMDA receptor-agonist D-cycloserine. This tDCS polarity-dependent alteration of NMDA receptor function seems to be initiated by the respective membrane potential shift and probably by the accompanying cortical activity modification,because it is prevented by the sodium channel blocker carbamazepine. Intraneuronal calcium concentration also contributes, because calcium channel antagonists eliminate the excitability-enhancing aftereffects of anodal tDCS. Recently, tDCS has been found to improve psychopathological symptoms (auditory hallucination in particular), cognitive deficits and insight of schizophrenia and also strengthen cardiac autonomic function in healthy subjects. Further replication studies are needed.
The study aimed to investigate whether transcranial direct current stimulation could modify auditory hallucination, insight, neurocognitive function, heart rate variability, psychosocial functioning and quality of life in patients with schizophrenia.
Study design: randomized double-blind, sham-controlled study design.
Participants: 60 patients having a diagnosis of schizophrenia or schizoaffective with refractory auditory verbal hallucinations (defined as the persistence of daily auditory verbal hallucinations without remission in spite of antipsychotic medications at an adequate dosage for at least 3 months), aged 20-65 years.
Others: see Arms and Interventions, Eligibility Criteria or Outcome Measures.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Direct current (DC) generated by a DC stimulator (Eldith DC stimulator: www. neuroconn.de/dc-stimulator_plus_en/) was bilaterally delivered through a pair of saline-soaked surface sponge electrodes (35 square centimeter). The anode was placed with the middle of the electrode over a point midway between F3 and FP1 (left dorsolateral prefrontal cortex and left prefrontal cortex). The cathode was located over a point midway between T3 and P3 (left temporo-parietal junction). Stimulation was applied at an intensity of 2 mA for 20 min, twice-daily on 5 consecutive weekdays. The twice daily sessions were separated by at least 3 hours.
| Arm | Type | Receives |
|---|---|---|
| Active tDCS | Active comparator | Device: tDCSDirect current (DC) generated by a DC stimulator (Eldith DC stimulator: www. neuroconn.de/dc-stimulator_plus_en/) was bilaterally delivered through a pair of saline-soaked surface sponge electrodes (35 square centimeter). The anode was placed with the middle of the electrode over a point midway between F3 and FP1 (left dorsolateral prefrontal cortex and left prefrontal cortex). The cathode was located over a point midway between T3 and P3 (left temporo-parietal junction). Stimulation was applied at an intensity of 2 mA for 20 min, twice-daily on 5 consecutive weekdays. The twice daily sessions were separated by at least 3 hours. All patients in the active tDCS group were maintained on their antipsychotic medications throughout the study period. |
| Sham tDCS | Sham comparator | Device: tDCSIn sham stimulation, the current was turned on for 30 sec and then ramped down to 0 mA. All patients in the sham tDCS group were maintained on their antipsychotic medications throughout the study period. |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients who met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder were included in the study. All these patients showed refractory auditory verbal hallucinations,which are defined as the persistence of daily auditory verbal hallucinations without remission in spite of antipsychotic medications at an adequate dosage for at least 3 months.
Key exclusion criteria (5 listed)
- Pregnancy or breastfeeding.
- Having epilepsy, severe physical illness, any current psychiatric comorbidity or history of substance dependence.
- Having contraindications for transcranial electrical/magnetic stimulation.
- Having intracranial metal foreign bodies.
- Having a history of intracranial neoplasms or surgery, or a history of severe head injuries or cerebrovascular diseases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tDCS | Device | Active tDCS, Sham tDCS |
Primary outcome
Changes from baseline scores of Auditory Hallucination Rating Scale (AHRS) at the timepoint immediately after tDCS, at one month and three months after tDCS.
Time frame: Three months.
A clinician-administered rating scale to measure the severity of auditory (verbal) hallucination of the patients with schizophrenia spectrum disorder.
14 secondary outcomes
Changes from baseline scores of Positive and Negative Syndrome Scale (PANSS) at the timepoint immediately after tDCS, at one month and three months after tDCS.
Time frame: Three months.
Changes from baseline scores at Personal and Social Performance scale (PSP) at the timepoint immediately after tDCS, at one month and three months after tDCS.
Time frame: Three months.
Changes from baseline results of Digit span (forward and backward)
Time frame: One month.
Changes from baseline results of Finger tapping test
Time frame: One month.
Changes from baseline results of Continuous Performance (CPT, version 2.0)
Time frame: One month.
Changes from baseline results of Wisconsin Card Sorting Test (WCST) at the timepoint immediately after tDCS and at one month after tDCS.
Time frame: One month.
Changes from baseline results of Trail Making Test (TMT) at the timepoint immediately after tDCS and at one month after tDCS.
Time frame: One month.
Changes from baseline results of Tower of London test at the timepoint immediately after tDCS and at one month after tDCS.
Time frame: One month.
Changes from baseline heart rate variability (HRV) at the timepoint immediately after tDCS and at one month after tDCS.
Time frame: One month.
Changes from baseline scores of the brief version of questionnaire of The World Health Organization Quality of Life (WHOQOL-BREF Taiwan version) at the timepoint immediately after tDCS and at one month after tDCS.
Time frame: One month.
Changes from baseline scores of self-reported version of the graphic Personal and Social Performance scale (SRG-PSP) at the timepoint immediately after tDCS and at one month after tDCS.
Time frame: One month.
Changes from baseline scores of the abbreviated version of the Scale to Assess Unawareness in Mental Disorder in schizophrenia (SUMD) at the timepoint immediately after tDCS, at one month and three months after tDCS.
Time frame: Three months.
Changes from baseline scores of the Taiwanese version of the Beck Cognitive Insight Scale (BCIS) at the timepoint immediately after tDCS and at one month after tDCS.
Time frame: One month.
Changes from baseline scores of the Taiwanese version of the Self- Appraisal of Illness Questionnaire (SAIQ) at the timepoint immediately after tDCS and at one month after tDCS.
Time frame: One month.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hsin-An Chang, M.D. principal investigator
Tri-Service General Hospital, National Defense Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing tDCS in people with Schizophrenia and Schizoaffective Disorder, run by Tri-Service General Hospital (TSGH) at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes from baseline scores of Auditory Hallucination Rating Scale (AHRS) at the timepoint immediately after tDCS, at one month and three months after tDCS. (time frame: Three months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2018.