Clinical trial NCT03701100: The Effects of Bimodal tDCS on Illness Severity, Insight, Functional Outcomes, Neurocognition and HRV in Schizophrenia
Official title: The Effects of Bimodal Anodal Transcranial Direct Current Stimulation Over Bilateral Prefrontal Cortex on Illness Severity, Insight, Functional Outcomes, Quality of Life, Neurocognition and Heart Rate Variability (HRV) in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Insight Impaired
Psychotic Symptoms
Schizoaffective Disorder
Neurocognitive Dysfunction
Autonomic Imbalance
Psychosocial Impairment
Quality of Life
Lead sponsor: Tri-Service General Hospital
Sponsor class: OTHER
First posted: 2018-10-09
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 Eldith DC stimulator was bilaterally delivered through a pair of saline-soaked surface sponge electrodes (35 square centimeter). One anode was placed with the middle of the electrode over a point midway between International 10-20 electrode positions F3 and Fp1 (left dorsolateral prefrontal cortex and left prefrontal cortex). The other was located over a point midway between F4 and Fp2 (right dorsolateral prefrontal cortex and left prefrontal cortex). An extracephalic positions were used for the reference electrodes (cathodes) in order to avoid confounding effects from inhibitory cathodal effects at other cortical sites. The reference electrodes were placed on bilateral forearms. Stimulation was applied at an intensity of 2 milliampere (mA) (current density=1.14 A/square meter) for 20 min, twice-daily on 5 consecutive weekdays (total charge density=2736 C/square meter).
Primary purpose: TREATMENT

Brief summary: The study aimed to investigate the effects of bimodal anodal transcranial direct current stimulation (tDCS) over bilateral dorsolateral prefrontal cortex (DLPFC) on psychopathological symptoms, insight, psychosocial functioning, neurocognitive function and heart rate variability (HRV) in schizophrenia patients

Detailed description: Transcranial direct current stimulation 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 N-methyl-D-aspartate (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 after-effects of anodal tDCS. Recently, unimodal anodal tDCS over left dorsolateral prefrontal cortex (DLPFC) has been found to improve psychopathological symptoms, cognitive deficits and insight of schizophrenia and also strengthen cardiac autonomic function in healthy subjects. Further studies using bimodal anodal tDCS over bilateral dorsolateral prefrontal cortex (DLPFC) and prefrontal cortex are needed.

Study design: randomized double-blind, sham-controlled study design.

Participants: 60 patients having a diagnosis of schizophrenia or schizoaffective were randomly allocated to receive 20 minutes of active 2-mA tDCS or sham stimulation twice a day on 5 consecutive weekdays. These participants were assessed at baseline, after intervention and in a three-months follow-up.

Active or sham stimulation: The present study used bimodal anodal tDCS over bilateral dorsolateral prefrontal cortex (DLPFC) and prefrontal cortex. One anode was placed with the middle of the electrode over a point midway between International 10-20 electrode positions F3 and Fp1 (left dorsolateral prefrontal cortex and left prefrontal cortex). The other was located over a point midway between F4 and Fp2 (right dorsolateral prefrontal cortex and left prefrontal cortex). An extracephalic positions were used for the reference electrodes (cathodes) in order to avoid confounding effects from inhibitory cathodal effects at other cortical sites. The reference electrodes were placed on bilateral forearms.

Others: see Arms and Interventions, Eligibility Criteria or Outcome Measures.

Eligibility criteria: Inclusion Criteria:

1. Eligible participants aged 20-65 with DSM-IV-TR-defined schizophrenia or schizoaffective disorder.
2. Duration of illness ≧ 1 year.
3. Being on an adequate therapeutic dose of antipsychotics and clinically stable (nonacute phase of illness) but symptomatic for at least 4 weeks prior to enrolment as defined by Clinical Global Impression-Severity of Illness scale (CGI-S) score ≦ 4 (at both screening and baseline).
4. Agreement to participate in the study and provide the written informed consent.

Exclusion Criteria:

1. Having current psychiatric comorbidity or active substance use disorder, in exception to caffeine and/or tobacco.
2. Having history of seizures.
3. Having contraindications for tDCS, e.g., implanted brain medical devices or metal in the head.
4. Having history of intracranial neoplasms or surgery, or a history of severe head injuries or cerebrovascular diseases.
5. Pregnancy or breastfeeding at enrollment.

Primary 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
Secondary outcomes:
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 scores of the Global Assessment of Functioning (GAF) Scale of the DSM-IV at the timepoint immediately after tDCS, at one month and three months after tDCS.
timeFrame: Three months.
measure: Changes from baseline scores of the Clinical Global Impression (CGI) rating scales at the timepoint immediately after tDCS, at one month and three months after tDCS.
timeFrame: Three months.
measure: Changes from baseline scores of the 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.
measure: Changes from baseline scores of the self-administered WHOQOL-BREF at the timepoint immediately after tDCS and at one month after tDCS.
timeFrame: One month.
measure: Changes from baseline results of Digit span (forward and backward) at the timepoint immediately after tDCS and at one month after tDCS.
timeFrame: One month
measure: Changes from baseline results of Finger tapping test at the timepoint immediately after tDCS and at one month after tDCS.
timeFrame: One month
measure: Changes from baseline results of Continuous Performance (CPT, version 2.0) at the timepoint immediately after tDCS and at one month after tDCS.
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 Mini-Mental State Examination (MMSE) at the timepoint immediately after tDCS, at one month and three months after tDCS.
timeFrame: Three months.
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:
citation: Chang CC, Kao YC, Chao CY, Tzeng NS, Chang HA. Examining bi-anodal transcranial direct current stimulation (tDCS) over bilateral dorsolateral prefrontal cortex coupled with bilateral extracephalic references as a treatment for negative symptoms in non-acute schizophrenia patients: A randomized, double-blind, sham-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jan 10;96:109715. doi: 10.1016/j.pnpbp.2019.109715. Epub 2019 Jul 27.