The Effects of Bimodal tDCS on Illness Severity, Insight, Functional Outcomes, Neurocognition and HRV in Schizophrenia

NCT ID: NCT03701100

Last Updated: 2018-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-17
• Study Completion Date: 2018-09-21

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.

Conditions

Schizophrenia; Insight Impaired; Psychotic Symptoms; Schizoaffective Disorder; Neurocognitive Dysfunction; Autonomic Imbalance; Psychosocial Impairment; Quality of Life

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Active tDCS

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). The reference electrodes were placed on bilateral forearms. Stimulation was applied at an intensity of 2 mA for 20 min, twice-daily on 5 consecutive weekdays. All patients in the active tDCS group were maintained on their antipsychotic medications throughout the study period.

Group Type: ACTIVE_COMPARATOR

tDCS

Intervention Type: DEVICE

tDCS

Sham tDCS

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.

Group Type: SHAM_COMPARATOR

tDCS

Intervention Type: DEVICE

tDCS

Interventions

tDCS

tDCS

Intervention Type: DEVICE

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tri-Service General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hsin-An Chang, MD

Attending Psychiatrist, Department of Psychiatry, Principal Investigator, Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hsin-An Chang, M.D.

Role: PRINCIPAL_INVESTIGATOR

Tri-Service General Hospital, National Defense Medical Center

Locations

Tri-service general hospital

Taipei, , Taiwan

Countries

Taiwan

References

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.

Reference Type: DERIVED

PMID: 31362034 (View on PubMed)

Other Identifiers

2-103-03-002-3

Identifier Type: -

Identifier Source: org_study_id