Study of Repetitive Transcranial Magnetic Stimulation in the Treatment of Cognitive Impairment in Schizophrenia

1. Exploration of repetitive transcranial magnetic stimulation（rTMS）on working memory and cognitive impairment symptoms of schizophrenia treatment and mechanism.
2. Analysis of high-frequency repetitive transcranial magnetic stimulation stimulation to the improvement of negative symptoms and psychotic symptoms.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Device: Repetitive Transcranial Magnetic Stimulation

Detailed Description

The study was a randomized double-blind sham-controlled trial for 4 weeks. Patients with schizophrenia were treated with 20-Hz rTMS for 4 weeks to the left dorsolateral prefrontal cortex (added to the ongoing treatment). Negative symptoms were assessed with the Scale for the Assessment of Negative Symptoms (SANS), the Positive and Negative symptom scale (PANSS).The auditory steady state responses (ASSR) were obtained for the assessment of gamma oscillation.And cognitive symptoms were assessed by MATRICS cognitive test battery (MCCB) Chinese version and n-back task.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1）patients to be diagnosed according to the Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders(DSM-IV) for paranoid schizophrenia；2）20～49 years old；3）Duration of 2 ~ 10 years;4）the disease situation is stable， the fluctuation of Positive and Negative Symptom Scale（PANSS）total score ≤10% in last 1 month, and have accepted the current drugs for more than 8 weeks; 5）Patients, their families and doctors are agreed that the disease situation is stable and maintained current drug treatment in next month；6）Signed an informed consent

Exclusion Criteria:

• 1)patients to be diagnosed according to DSM-IV for substance abused,development delayed;2)suffering from serious physical disease and can not accept the treatment;3)repetitive transcranial magnetic stimulation(rTMS) contraindications: intracranial metal substance, with heart pacemakers and cochlear implants, intracranial pressure;4)the disease situation is not stable， the fluctuation of Positive and Negative Symptom Scale（PANSS）total score >10% in last 1 month, Positive and Negative Symptom Scale（PANSS）total score > 60;5)difficult to maintain the current drug treatment for at least 1 month;6）undergoing electroconvulsive therapy（ECT）in last 3 months.

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 rTMS; Active treatment will be delivered at an intensity that is 90% of the resting motor threshold (RMT). Stimulation will be delivered at 20 Hz with 100 stimulation trains of 20 stimuli each (i.e., 2000 stimuli) and an inter-train interval of 9 sec. Treatment will be applied in sequential order to the left dorsolateral prefrontal cortex (DLPFC). Intervention: Device: Repetitive Transcranial Magnetic Stimulation	Device: Repetitive Transcranial Magnetic Stimulation; The MagPro X100 is connected to a Magnetic Coil which transfers the magnetic stimulation to the tissue. The original coils MC-B65 can be used with the MagPro X100.
Sham Comparator: Sham rTMS; Sham rTMS stimulation will be delivered using the same stimulation parameters and at the site of active treatment, but the coil will be reversed. This method produces sound and some somatic sensation (e.g., contraction of scalp muscles) similar to those of active stimulation, but with minimal direct brain effects.Intervention: Device: Repetitive Transcranial Magnetic Stimulation	Device: Repetitive Transcranial Magnetic Stimulation; The MagPro X100 is connected to a Magnetic Coil which transfers the magnetic stimulation to the tissue. The original coils MC-B65 can be used with the MagPro X100.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Change in the Severity of Negative Symptoms	The assessment of negative symptoms were measured with the Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS).The SANS contains 30 particular items divided into 5 symptomatological domains: 1) affective flattening and/or blunting, 2) alogia, 3) avolition and/or apathy, 4) anhedonia, and 5) impaired attention. Each item is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 150. Higher scores indicate more impairment.The PANSS contains 30 particular items divided into 3 subscores: 1)positive, 2) negative, and 3) general subscore. Each item is scored on a scale from 1 (absent) to 7 (extreme) with a total scoring range of 30 to 210. Higher scores indicate more impairment. The primary outcomes were the changes in the severity of negative symptoms as measured with SANS total score and PANSS negative subscore after 4 weeks of intervention.	Baseline, after 4 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MATRICS Consensus Cognitive Battery (MCCB) in Chinese Version	MCCB in Chinese Version includes 9 tasks across 7 domains, and a composite score, including Processing Speed (Brief Assessment of Cognition in Schizophrenia Symbol Coding, Animal Fluency, Trails A), Attention (Continuous Performance Test), Working Memory (WMS-III Spatial Span), Verbal Learning (Hopkins Verbal Learning Test - Revised), Visual Learning (Brief Visuospatial Memory Test - Revised), Problem Solving (Neuropsychological Assessment Battery), and Social Cognition (Mayer-Salovey- Caruso Emotional Intelligence Test).The results are reported as T scores with a mean of 50 and an SD of 10.	Baseline and 4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-related Spectral Perturbation (ERSP)	Alterations in gamma-band ASSR have been thought to be the most robust finding of abnormal neural oscillations in patients with schizophrenia. EEG data were acquired using a 64-electrode cap and alternating current BrainAmp amplifiers (Brain Products GmbH, Germany). We used EEGLAB to perform time-frequency analysis with a short-term Fourier transformation, and then calculated ERSP.	4 weeks

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Investigators: Study Director: Dengtang Liu, MD, Chief Psychiatrist and Professor

Publications and helpful links

General Publications

• Zhuo K, Tang Y, Song Z, Wang Y, Wang J, Qian Z, Li H, Xiang Q, Chen T, Yang Z, Xu Y, Fan X, Wang J, Liu D. Repetitive transcranial magnetic stimulation as an adjunctive treatment for negative symptoms and cognitive impairment in patients with schizophrenia: a randomized, double-blind, sham-controlled trial. Neuropsychiatr Dis Treat. 2019 May 8;15:1141-1150. doi: 10.2147/NDT.S196086. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2013
• Primary Completion (Actual): December 31, 2014
• Study Completion (Actual): January 31, 2015

Study Registration Dates

• First Submitted: September 9, 2013
• First Submitted That Met QC Criteria: September 9, 2013
• First Posted (Estimate): September 12, 2013

Study Record Updates

• Last Update Posted (Actual): October 29, 2018
• Last Update Submitted That Met QC Criteria: February 12, 2018
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: schizophrenia
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Cognition Disorders; Schizophrenia; Cognitive Dysfunction
• Other Study ID Numbers: 11ZR1431600

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
• product manufactured in and exported from the U.S.: No