Developing Dual-channel Transcranial Alternating Current Stimulations Targeting Negative Symptoms in Schizophrenia

Dual-channel Transcranial Alternating Current Stimulations Targeting Negative Symptoms in Schizophrenia Patients: a Randomized Clinical Trial

Negative symptoms are core symptoms in schizophrenia which play an important role in clinical outcomes and impede patients to return to society. Anti-psychotic medicines have shown limited effect in improving negative symptoms and cognitive functioning, whereas non-invasive neuromodulations, i.e. , transcranial alternating current stimulation (tACS), have shown promising potentials. Recently new evidence of brain structural and functional alterations has been provided by neuroimaging studies. Brady RO et al. found cerebellar-prefrontal network connectivity was related to negative symptoms in schizophrenia. It provides clues for developing a new tACS protocol targeting improving negative symptoms, in which dual-channel high-density alternating current stimulations were delivered over both the right dorsolateral prefrontal cortex and cerebellum simultaneously.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Transcranial Alternating Current Stimulations; Negative Symptoms
• Intervention / Treatment: Device: transcranial alternating current stimulation (NE Starstim)

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Zhenjiang, Jiangsu, China
      • Zhengjiang Mental Health Center
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Mental Health Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• meet the DSM-V diagnostic criteria for schizophrenia;
• present with prominent negative symptoms with PANSS-negative scores >20, at least one score of PANSS N1-N7 >3, and reductive ratio of PANSS-negative in the past two weeks before recruitment <10%;
• stable usage and dosage of anti-psychotic medicines in the past two weeks and during the tACS intervention.
• age within 18-60;
• illness duration >1year;
• education at least 6 years;
• written consent of receiving tACS intervention.

Exclusion Criteria:

• Meet any DSM-V diagnostic criteria of any other psychiatric disorders besides schizophrenia ;
• any history of alcohol or substance dependence in the past 3 months;
• any other major physical disease (i.e., Sensorimotor disorder, neurological disease);
• any metal implants or any other tACS contraindication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active tACS; Active tACS will be applied twice daily for 5 days. In each session, dual-channel high-density theta(7Hz) tACS stimulations will be delivered over the right DLPFC (one anodal electrode at F4, between -1.2mA and 1.2 mA; two cathodal electrodes at AF4 and FC6, between -0.6mA and 0.6mA) and cerebellum (one anodal electrode at Oz, between -1 mA and 1mA; two cathodal electrodes at PO3 and PO4, between -0.5mA and 0.5mA) lasting 20 minutes.	Device: transcranial alternating current stimulation (NE Starstim); dual-channel theta-tACS over right DLPFC and cerebellum simultaneously
Sham Comparator: Sham tACS; Sham tACS will be also applied twice daily for 5 days.The parameters of tACS electrodes numbers, locations, and current duration are all the same with active tACS. But sham tACS begin with a fade in over 3s to the peak, followed immediately by no current stimulation for 20 minutes and a fade out of 3s.	Device: transcranial alternating current stimulation (NE Starstim); dual-channel theta-tACS over right DLPFC and cerebellum simultaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
reductive ratio of PANSS-negative symptoms scores	differences of reductive ratio of PANSS-negative symptoms scores after between active and sham tACS	At 1 week and 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes of PANSS total scores	changes of PANSS total scores before and after active or sham tACS	At 1 week and 3 weeks
changes of P300 activity	changes of P300 activity at baseline and after 10-session tACS	At 1 week
changes of MMN activity	changes of MMN activity at baseline and after 10-session tACS	At 1 week
changes of power of resting-state EEG activity	changes of power of resting-state EEG activity at baseline, after 1-session tACS and after 10-session tACS	At 1 day and 1 week
centroid value from fNIRS recording before and after active or sham tACS	centroid value from fNIRS recording before and after active or sham tACS	At 1 week
Integral value from fNIRS recording before and after active or sham tACS	Intergral value from fNIRS recording before and after active or sham tACS	At 1 week
cognitive functioning changes using MCCB	changes of MCCB scores before and after active or sham tACS	At 1 week and 3 weeks

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Investigators: Principal Investigator: Yingying Tang, PhD, Shanghai Mental Health Center; Principal Investigator: Jianhua Sheng, PhD, Shanghai Mental Health Center

Publications and helpful links

General Publications

• Reinhart RMG, Nguyen JA. Working memory revived in older adults by synchronizing rhythmic brain circuits. Nat Neurosci. 2019 May;22(5):820-827. doi: 10.1038/s41593-019-0371-x. Epub 2019 Apr 8.
• Brady RO Jr, Gonsalvez I, Lee I, Ongur D, Seidman LJ, Schmahmann JD, Eack SM, Keshavan MS, Pascual-Leone A, Halko MA. Cerebellar-Prefrontal Network Connectivity and Negative Symptoms in Schizophrenia. Am J Psychiatry. 2019 Jul 1;176(7):512-520. doi: 10.1176/appi.ajp.2018.18040429. Epub 2019 Jan 30.
• Smith RC, Md WL, Wang Y, Jiang J, Wang J, Szabo V, Faull R, Jin H, Davis JM, Li C. Effects of transcranial direct current stimulation on cognition and symptoms in Chinese patients with schizophrenia✰. Psychiatry Res. 2020 Feb;284:112617. doi: 10.1016/j.psychres.2019.112617. Epub 2019 Nov 2.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): July 31, 2024
• Study Completion (Actual): July 31, 2024

Study Registration Dates

• First Submitted: April 1, 2021
• First Submitted That Met QC Criteria: April 23, 2021
• First Posted (Actual): April 26, 2021

Study Record Updates

• Last Update Posted (Estimated): December 12, 2024
• Last Update Submitted That Met QC Criteria: December 8, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia
• Other Study ID Numbers: 20191836

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We will decide IPD or not when the clinical trial is completed.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No