Transcranial Alternating Current Stimulation (tACS) for Cognitive Impairments in Patients With Schizophrenia

Transcranial Alternating Current Stimulation (tACS) for Cognitive Impairments in Patients With Schizophrenia: a Randomized Controlled Trial

This trial attempts to investigate whether 10 sessions of tACS improves cognitive function, especially which domains of cognitive function are most improved and to investigate whether 10 sessions of tACS affecting brain activation during a working memory task and changes patterns of brain connectivity networks.Subjects will be divided into 2 groups 2:1, active and sham tACS. 50 subjects will be in the active group, and 25 subjects in the sham group (specific numbers to be decided on later).

Study Overview

• Status: Unknown
• Conditions: Schizophrenia
• Intervention / Treatment: Device: Active tACS; Device: Active boosting; Device: Sham boosting; Device: Sham tACS

Detailed Description

Schizophrenia patients (SZ) show profound and persistent cognitive deficits in attention, executive processing, and verbal and visuospatial memory, which persist even after psychotic symptoms are ameliorated. Cognitive deficits may be more important in preventing functional, occupational, and social recovery in SZ than other symptom domains and are not effectively treated by current pharmacological approaches. Alternating current stimulation (tACS) is less expensive than other modalities (e.g. repetitive transcranial magnetic stimulation; rTMS), easily available, and has a good safety profile in healthy controls (HC) and SZ. The ability to entrain γ oscillations with 40Hz tACS, might compensate more specifically for this deficit in γ oscillations in schizophrenia, and, may therefore, produce more robust behavioral improvements in working memory and other aspects of cognition.However, no studies have looked at the effects of multiple daily tACS stimulation at a 40HZ γ frequency on cognitive function and symptoms in schizophrenia. This provides a rationale for the current study, which proposes to investigate the effects of 10 sessions of 40HZ tACS on cognitive functions, symptoms in schizophrenia.

Active vs. sham treatment will be randomly assigned in a 2:1 fashion (A:S) in groups using computer generated lists. Subjects and tDCS testers or evaluators will be blind to treatment. Subjects will be evaluated with cognitive, symptom and functional measures at baseline, within 1 day ( or 2 days fro some measures) after 10 sessions, 2 weeks after 10 sessions, 1 month after 10 sessions, and 2 months after 10 sessions.After the 1 month evaluation, subjects in the initial active tACS group will be randomly assigned to receive either 5 booster sessions of either active or sham tACS ( 25 subjects each), following parameters used in the initial treatment. Subjects in the initial Sham group will receive 5 booster session Sham tACS. Participants will be scanned once prior to tACS sessions, and within 3 days after the 10th tACS session, using our Siemens 3T Tim Verio MRI scanner with a standard 32-channel phased-array head coil.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Shanghai Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who have cognitive deficits as indicated by a score of < 85 on RBANS, and meet criteria for DSM-5 diagnosis of chronic SZ, schizoaffective disorder (SA), or schizophreniform disorder (SZF), and who are stably treated with antipsychotic medications and are not in acute exacerbation of illness symptoms.

Exclusion Criteria:

• Patients with risk factors for an MRI scan, seizure disorder, and for women of childbearing age who are pregnant or regularly engaging in sexual activity and not regularly using an acceptable birth control method (systemic or double-barrier).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active tACS & active boosting group; The active tACS & active boosting group will be stimulated with 10 sessions of active alternating current stimulation (tACS) and 5 booster sessions of active tACS.	Device: Active tACS; Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded). Each subject will have 10 active tACS sessions.The active tACS group will be stimulated with a 2 mA current for 20 minutes.; Device: Active boosting; Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded).One month later after initial treatment, each subject will have 5 booster sessions of active tACS.The active boosting group will be stimulated with a 2 mA current for 20 minutes.
Other: Active tACS & sham boosting group; The active tACS & sham boosting group will be stimulated with 10 sessions of active alternating current stimulation (tACS) and 5 booster sessions of sham tACS.	Device: Active tACS; Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded). Each subject will have 10 active tACS sessions.The active tACS group will be stimulated with a 2 mA current for 20 minutes.; Device: Sham boosting; Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded).One month later after initial treatment, each subject will have 5 booster sessions of sham tACS.The sham boosting group will have stimulation lasting only 40 seconds though the electrodes will remain in place for 20 min.
Sham Comparator: Sham tACS & sham boosting group; The sham tACS & sham boosting group will be stimulated with 10 sessions of sham alternating current stimulation (tACS) and 5 booster sessions of sham tACS.	Device: Sham boosting; Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded).One month later after initial treatment, each subject will have 5 booster sessions of sham tACS.The sham boosting group will have stimulation lasting only 40 seconds though the electrodes will remain in place for 20 min.; Device: Sham tACS; Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded). Each subject will have 10 sham tACS sessions.The sham tACS group will have stimulation lasting only 40 seconds though the electrodes will remain in place for 20 min.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in The MATRICS Consensus Cognitive Battery (MCCB)		Change from Baseline MCCB at 2 weeks.
changes in Neuroimage changes in Magnetic Resonance Imaging (MRI)	Including T1, resting state functional MRI, task based functional MRI and Diffusion Tensor Imaging(DTI)	Change from Baseline at 2 weeks.
changes in Gamma oscillation intensity ( 40-80 Hz) over the left and right frontal lobe	measured by electroencephalogram (EEG)	Change from Baseline at 2 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
N-back task	to test working memory	At baseline,1-week, 2-week, 4-week, and 8-week follow-up.
The Paced Auditory Serial Addition Task (PASAT)	to test Verbal Working memory	At baseline,2-week, 4-week, and 8-week follow-up.
The Positive and Negative Syndrome Scale (PANSS)	PANSS was assessed using 30 basic items to form three subscales: positive, negative, and general psychopathological scales.The value of each item is ranging from 1 to 7, higher values represent more serious symptoms of schizophrenia.	At baseline,2-week, 4-week, and 8-week follow-up.
The USCD Performance- Based Skills Assessment Battery (UPSA)		At baseline,2-week, 4-week, and 8-week follow-up.
Side-effects of tACS		At each stimulation session,up to 2 weeks.
The MATRICS Consensus Cognitive Battery (MCCB)		At 4-week and 8-week follow-up.

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Investigators: Principal Investigator: Chunbo Li, Ph.D., Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): March 1, 2020

Study Registration Dates

• First Submitted: October 27, 2018
• First Submitted That Met QC Criteria: November 26, 2018
• First Posted (Actual): November 28, 2018

Study Record Updates

• Last Update Posted (Actual): November 28, 2018
• Last Update Submitted That Met QC Criteria: November 26, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: cognition; schizophrenia; fMRI; tACS
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Cognition Disorders; Schizophrenia; Cognitive Dysfunction
• Other Study ID Numbers: 2018-24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No