Clinical trial NCT05582980: Online HD-tDCS Over the Left DLPFC During a Working Memory Task for Treating Negative Symptoms of Schizophrenia
Official title: Online High-definition Transcranial Direct Current Stimulation Over the Left Dorsolateral Prefrontal Cortex During a Working Memory Task for Treating Negative Symptoms of Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Schizoaffective Disorder, Mixed Type
Negative Symptoms in Schizophrenia
Keywords: Schizophrenia
Negative Symptoms
Dorsolateral prefrontal cortex
HD-tDCS
Working memory tasks
Lead sponsor: Tri-Service General Hospital
Sponsor class: OTHER
First posted: 2022-10-17
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
Primary purpose: TREATMENT

Brief summary: In this randomized double-blind trial, the investigators aim to investigate whether online high definition transcranial direct current stimulation (HD-tDCS) over the left dorsolateral prefrontal cortex (DLPFC) during a working memory task improves the severity of negative symptoms in schizophrenia patients with predominant negative symptoms.

Detailed description: Positive (delusions and hallucinations) and negative (blunted affect, avolition-apathy, alogia and anhedonia-asociality) symptoms are recognized as core features of schizophrenia. Antipsychotic medications as the first-line treatment for schizophrenia can reduce the positive symptoms within 14-28 days but good evidence that antipsychotics have any beneficial effect on negative symptoms is scarce. Negative symptoms remain the most important unmet therapeutic needs in schizophrenia.

Accumulating functional neuroimaging research has linked the correlation between negative symptoms and reduced dorsolateral prefrontal activity. Atypical antipsychotics, the mainstream treatment for schizophrenia, are known to show little effect on patients' hypofrontality and some of them (e.g., strong dopamine receptor antagonists and clozapine) are even associated with a decrease in prefrontal activation. All these findings have driven the development of novel and effective treatments targeting the brain regions implicated in negative symptoms of schizophrenia, e.g., non-invasive brain stimulation (NIBS) of over the left DLPFC.

Transcranial direct current stimulation (tDCS) is a NIBS that has great potential to improve negative symptoms of schizophrenia. tDCS applies a weak direct current on the scalp and through the brain and rapidly leads to changes in cortical excitability by shifting membrane resting potentials, which facilitates either depolarization or hyperpolarization of the brain neurons. Repetitive stimulation during specific time intervals further enhances efficacy and prolongs the after-effects of tDCS through modifying the efficacy of N-methyl-D-aspartate receptor. An increasing number of studies attempted to reduce negative symptoms of schizophrenia by using tDCS.

Most tDCS research delivers direct current to the participants while they are at rest (offline tDCS). There has been a novel stimulation model called "online" stimulation, in which non-invasive brain stimulation is applied while the individuals are concurrently engaged in a neuropsychological task. For example, a cognitive task has been known to activate a specific brain region (e.g., working memory task and prefrontal cortex). The susceptibility of a specific brain region (i.e., prefrontal cortex) to neuro-stimulation will be enhanced if it is simultaneously activated when engaging a working memory task. Compared to the use of tDCS while the subject is at rest (offline tDCS), the application of tDCS to activate the prefrontal cortex while the subject is engaged in a working memory task (online tDCS) can potentially result in resonated effects and further enhance the neuromodulation on the target brain region, aka functional targeting.

High definition tDCS (HD-tDCS) targets cortical areas using arrays of electrodes on the scalp (i.e. a classic 4 × 1 ring configuration) and constrains the electrical current flow to a specific cortical area, allows for more accurate definition of the current field distribution than conventional tDCS and serves to optimize electrode montage to specifically target the brain areas of interest.

Our proof-of-concept study aims to investigate the efficacy of online HD-tDCS over left DLPFC as an add-on therapy to improve negative symptoms severity in schizophrenia patients with predominant negative symptoms. Moreover, it provides data on other secondary outcomes and preliminary neurophysiological data for this intervention condition.

Eligibility criteria: Inclusion Criteria:

* Subjects aged 20-65 years and diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ( DSM-5 ) schizophrenia or schizoaffective disorder
* Duration of illness≧1 year
* With a clinical presentation of predominant negative symptoms (according to the clinical judgment of 2 experienced psychiatrists) and the Positive and Negative Syndrome Scale (PANSS) score \> 70
* Receiving stable antipsychotic drug regimen \>8 weeks.

Exclusion Criteria:

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

Primary outcomes:
measure: The change over time in the Chinese version of the Positive and Negative Syndrome Scale Factor Score for Negative Symptoms (PANSS-FSNS) (from baseline to the timepoints immediately after intervention, at one-week and one-month follow-ups).
timeFrame: Five weeks
Secondary outcomes:
measure: The change over time in the score of the Chinese version of the Scale for the Assessment of Negative Symptoms (SANS) (from baseline to the timepoints immediately after intervention, at one-week and one-month follow-ups).
timeFrame: Five weeks
measure: The change over time in the scores of two subdomains of PANSS negative symptoms (from baseline to the timepoints immediately after intervention, at one-week and one-month follow-ups).
timeFrame: Five weeks
measure: The change over time in the scores of the five-factor PANSS model other than FSNS (from baseline to the timepoints immediately after intervention, at one-week and one-month follow-ups).
timeFrame: Five weeks
measure: The change over time in the score of the Chinese version of the Personal and Social Performance scale (PSP) (from baseline to the timepoints immediately after intervention, at one-week and one-month follow-ups).
timeFrame: Five weeks
measure: The change over time in the score of the self-reported version of the graphic personal and social performance scale (SRG-PSP) (from baseline to the timepoints immediately after intervention and at one-week follow-up)
timeFrame: Two weeks
measure: The change over time in the score of the abbreviated version of the Scale to Assess Unawareness in Mental Disorder in schizophrenia (SUMD) (from baseline to the timepoints immediately after intervention, at one-week and one-month follow-ups).
timeFrame: Five weeks
measure: The change over time in the score of the Taiwanese version of the Beck Cognitive Insight Scale (BCIS) (from baseline to the timepoints immediately after intervention and at one-week follow-up)
timeFrame: Two weeks
measure: The change over time in the score of the Taiwanese version of the Self-Appraisal of Illness Questionnaire (SAIQ) (from baseline to the timepoints immediately after intervention and at one-week follow-up)
timeFrame: Two weeks
measure: The change over time in the score of the Chinese version of the Schizophrenia Quality of Life Scale Revision Four (from baseline to the timepoints immediately after intervention and at one-week follow-up)
timeFrame: Two weeks
measure: The change over time in the scores of Taiwanese version of Medication Adherence Rating Scale (from baseline to the timepoints immediately after intervention and at one-week follow-up).
timeFrame: Two weeks
measure: The change over time in the total score of the Extrapyramidal Symptoms Rating Scale (from baseline to the timepoints immediately after intervention, at one-week and one-month follow-ups).
timeFrame: Five weeks
measure: The changes over time in the results of Digit span (forward and backward) (from baseline to the timepoints immediately after intervention and at one-week follow-up)
timeFrame: Two weeks
measure: The changes over time in the results of Finger tapping test (from baseline to the timepoints immediately after intervention and at one-week follow-up)
timeFrame: Two weeks
measure: The changes over time in the results of Continuous Performance (CPT, version 2.0) (from baseline to the timepoints immediately after intervention and at one-week follow-up)
timeFrame: Two weeks
measure: The changes over time in the results of Wisconsin Card Sorting Test (WCST) (from baseline to the timepoints immediately after intervention and at one-week follow-up).
timeFrame: Two weeks
measure: The changes over time in the results of Tower of London test (from baseline to the timepoints immediately after intervention and at one-week follow-up)
timeFrame: Two weeks
measure: The changes over time in the results of Color Trails Test (CTT) (from baseline to the timepoints immediately after intervention and at one-week follow-up)
timeFrame: Two weeks
measure: The changes over time in the results of Stroop Color Word Test (SCWT) (from baseline to the timepoints immediately after intervention and at one-week follow-up)
timeFrame: Two weeks
measure: The changes over time in indices of heart rate variability (HRV) measured at baseline, the end of stimulation, and 1-week follow-up.
timeFrame: Two weeks
measure: The changes over time in EEG absolute power and lag phase synchronization in the frontal electrodes in the delta, theta, alpha, beta and gamma range (from baseline to the end of stimulation).
timeFrame: One week
measure: The changes over time in high density near infrared spectroscopy (from baseline to the end of stimulation).
timeFrame: One week
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Tri-service general hospital
Study officials:
affiliation: Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
name: Hsin-An Chang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: