Clinical trial NCT03388554: The Effects of tDCS on Auditory Hallucination, Insight, Neurocognitive Function and HRV in Patients With Schizophrenia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Schizoaffective Disorder
Auditory Hallucination, Verbal
Neurocognitive Dysfunction
Autonomic Imbalance
Psychosocial Impairment
Quality of Life
Lead sponsor: Tri-Service General Hospital
Sponsor class: OTHER
First posted: 2018-01-03
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

- 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.

Exclusion Criteria:

1. Pregnancy or breastfeeding.
2. Having epilepsy, severe physical illness, any current psychiatric comorbidity or history of substance dependence.
3. Having contraindications for transcranial electrical/magnetic stimulation.
4. Having intracranial metal foreign bodies.
5. Having a history of intracranial neoplasms or surgery, or a history of severe head injuries or cerebrovascular diseases.

Primary outcomes:
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.
timeFrame: Three months.
Secondary outcomes:
measure: 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.
timeFrame: Three months.
measure: 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.
timeFrame: Three months.
measure: Changes from baseline results of Digit span (forward and backward)
timeFrame: One month.
measure: Changes from baseline results of Finger tapping test
timeFrame: One month.
measure: Changes from baseline results of Continuous Performance (CPT, version 2.0)
timeFrame: One month.
measure: Changes from baseline results of Wisconsin Card Sorting Test (WCST) at the timepoint immediately after tDCS and at one month after tDCS.
timeFrame: One month.
measure: Changes from baseline results of Trail Making Test (TMT) at the timepoint immediately after tDCS and at one month after tDCS.
timeFrame: One month.
measure: Changes from baseline results of Tower of London test at the timepoint immediately after tDCS and at one month after tDCS.
timeFrame: One month.
measure: Changes from baseline heart rate variability (HRV) at the timepoint immediately after tDCS and at one month after tDCS.
timeFrame: One month.
measure: 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.
timeFrame: One month.
measure: 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.
timeFrame: One month.
measure: 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.
timeFrame: Three months.
measure: 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.
timeFrame: One month.
measure: 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.
timeFrame: One month.
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Tri-service general hospital
Study officials:
affiliation: Tri-Service General Hospital, National Defense Medical Center
name: Hsin-An Chang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: