nTMS for Negative Symptom in Schizophrenia

Effectiveness of Navigated Transcranial Magnetic Stimulation (nTMS) of Left Supramarginal Gyrus for Negative Symptoms : A Double-blind, Randomized Controlled Trial

This research aims to test the effectiveness of Navigated transcranial magnetic stimulation (nTMS) of left Supramarginal Gyrus for negative symptoms. In this double-blind, randomized controlled trial, patients will be assigned to active iTBS experimental group or sham iTBS group. Treatment will last for 10 days, and data will be collected at baseline, 1 day and 1 month after treatment.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia
• Intervention / Treatment: Device: Intermittent theta burst stimulation(iTBS); Device: Sham stimulation

Detailed Description

This research aims to test the effectiveness of Navigated transcranial magnetic stimulation (nTMS) for negative symptoms in patients with schizophrenia. In this double-blind, randomized controlled trial, patients will be assigned to active iTBS experimental group or sham iTBS group. By using the TMS Navigation System, the iTBS will be targeted at the left Supramarginal Gyrus, and parameters are set to triplet 50Hz bursts, repeat at 5Hz, 2s seconds on and 8 seconds off, 1800 pulses per session, intensity of 90% resting motor threshold(RMT), total duration of 10 minutes.Both group will receive nTMS 5 times a day, total treatment for 10 days. Measurements included a pretreatment measurement session, 10 days of nTMS treatment, a post-treatment measurement, and a follow-up measurement 1 month after treatment. At baseline, data of demographic variables (such as sex, age, years of education, occupational status, social support) and disease characteristics (such as duration of illness, antipsychotic daily dose in chlorpromazine equivalents, family psychiatric history) will be collected.At baseline, the day of the end of treatment (day 11±1), 1 month after the treatment (day40±7) , data of outcomes (such as Positive and Negative Symptom Scale (PANSS) score,Negative Symptoms(SANS) score and other secondary outcomes) will be collected in order to test the effectiveness of nTMS. After completing the 1 month follow-up, patients may choose whether to continue follow-up , in order to observe the long-term effects of the treatment. However, they will not receive any further experimental interventions.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Renrong Wu, M.D., Ph.D.; Phone Number: 15874179855; Email: wurenrong2013@163.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410011
      • Recruiting
      • Mental Health Institute of Second Xiangya Hospital,CSU
      • Contact: Renrong Wu, M.D., Ph.D.; Phone Number: 15874179855; Email: wurenrong2013@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1.Clinical diagnosis of schizophrenia according to ICD-11.
• 2.Confirmation of the diagnosis of schizophrenia using the SCID-5-RV (DSM-5 Structured Clinical Interview for DSM-5 Disorders - Research Version).
• 3.Score more than 4 points on either item of negative symptoms (N1-N7).
• 4.Aged less than 60 years.

Exclusion Criteria:

• 1.Clinical diagnosis or SCID-5-RV assessment confirming neurodevelopmental disorders, bipolar and related disorders, substance use disorders (excluding alcohol and tobacco).
• 2.Presence of severe or acute physical illnesses, including traumatic brain injury, intracranial space-occupying or infectious diseases, acute cardiovascular diseases, acute respiratory system diseases, acute hematological disorders, etc.
• 3.Presence of clearly defined genetic diseases, including tuberous sclerosis, multiple sclerosis, Kleefstra syndrome, 22q11.2 deletion syndrome, Prader-Willi syndrome, Klinefelter syndrome (47,XXY), etc.
• 4.Contraindication for MRI examination or rTMS, such as metal implantation in the body, epilepsy, cochlear implants, etc.
• 5.Severe risk of self-injury or suicide
• 6.Other conditions where the researchers find unsuitable for the treatment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experimental group: active iTBS; Patients assigned to experimental group would receive treatment of active iTBS. 50 iTBS sessions (1,800 pulses per session, 50-minute intersession interval) were delivered 10 days at 90% resting motor threshold.	Device: Intermittent theta burst stimulation(iTBS); By using the TMS Navigation System, the iTBS will be targeted at the left Supramarginal Gyrus.iTBS will be performed using Magstim Rapid² stimulator, parameters are set to triplet 50Hz bursts, repeat at 5Hz, 2s seconds on and 8 seconds off, 1800 pulses per session, intensity of 90% resting motor threshold(RMT), total duration of 10 minutes.; Other Names: Navigated transcranial magnetic stimulation (nTMS)
Sham Comparator: control group: sham iTBS; Patients assigned to control group would receive treatment of sham iTBS. The iTBS mode in sham iTBS is as the same as the active iTBS, but would be delivered with the sham coil, which provides the sensation of TBS without enough magnetic energy to reach the cortex.	Device: Sham stimulation; Patients in sham group would receive the same intervention procedure as the active ITBS group, but the coil will be replaced with sham coil, which provides the sensation of TBS without enough magnetic energy to reach the cortex.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Scale for Assessment of Negative Symptoms(SANS) score	The SANS measures the severity of negative symptoms in schizophrenia. It contains 24 items, each item is scored from 0 to 5, higher score indicates more severe symptom. The SANS evaluates five dimensions of the negative symptoms, which are apathy, poverty of thought, abulia, social withdrawal and disorders of attention.	Baseline, the day of the end of treatment (day 11±1), 1 month after the treatment (day40±7)
Change in Positive and Negative Symptom Scale (PANSS) score	The PANSS measures positive symptoms, negative symptoms and general psychopathology. It contains 30 items, each item is scored from 1 to 7, higher score indicates more severe psychopathology in the dimension. Here the investigators use the Chinese version of the PANSS to evaluate the severity of symptoms in schizophrenia in different participant and different treatment phase. The investigators mainly focus on change in the total score of the negative symptoms.	Baseline, the day of the end of treatment (day 11±1), 1 month after the treatment (day40±7)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The data of head resting-state functional magnetic resonance imaging	All patients undergo head MRI scans in Siemens Trio 3.0T scanner. Resting functional MRI will be acquired based on Blood Oxygenation Level Dependent (BOLD) contrast. It can detect changes in blood oxygenation to analyze the change of brain function after intervention.	Baseline, the day of the end of treatment (day 11±1), 1 month after the treatment (day40±7)
Change in MATRICS Consensus Cognitive Battery (MCCB) score	The MCCB measures the cognitive function in schizophrenia and other neuropsychiatric diseases. It covers nine cognitive domains including attention, information processing speed, verbal learning and memory, visual learning and memory, spatial working memory, reasoning, problem solving, social cognition, executive function and fine motor. Raw scores are converted to scale scores, then to normalized T scores. T scores of seven domains and composite score are further calculated. The changes of scores at different follow up timepoint will be used for assessing the improvement of cognitive function (higher score means a better outcome).	Baseline, the day of the end of treatment (day 11±1), 1 month after the treatment (day40±7)
Change in Personal and Social Performance Scale (PSP) score	The PSP is a 100-point single-item rating scale that assesses four important domains of patients with mental disorders : (a) socially useful activities, including work and study, (b) personal and social relationships, (c) self-care, and (d) disturbing and aggressive behaviors. Higher score indicates better social function.	Baseline, the day of the end of treatment (day 11±1), 1 month after the treatment (day40±7)
Change in Global Assessment Function (GAF) score	The GAF is a 100-point single-item rating scale that evaluate level of patients with schizophrenia, combining the level of social function and the severity of psychiatric symptoms to produce a single score. Higher score indicates better social function.	Baseline, the day of the end of treatment (day 11±1), 1 month after the treatment (day40±7)
Change of electroencephalogram	Neuroscan multi-channel evoked potential workstation records EEG data, using the international 10-20 system for electrode placement, with Ag/AgCl electrodes on a 64/128 electrode cap.	Baseline, first day of treatment (day 1), the day of the end of treatment (day 11±1), 1 month after the treatment (day40±7)
Change of TMS-EEG (Transcranial Magnetic Stimulation Electroencephal	Neuroscan multi-channel evoked potential workstation records EEG data, using the international 10-20 system for electrode placement, with Ag/AgCl electrodes on a 64/128 electrode cap. During TMS-EEG recording, stimulation of 100 single TMS pulses were delivered at 100% RMT intensity while participants remained at rest with their eyes open.	Baseline, the day of the end of treatment (day 11±1), 1 month after the treatment (day40±7)
Change in Montgomery-Asberg Depression Rating Scale (MADRS) score	MADRS is a 10-item scale that measures the severity of depression symptoms. Each item is scored from 0 to 6, higher score indicates more severe symptom.	Baseline, the day of the end of treatment (day 11±1), 1 month after the treatment (day40±7)
Change in Calgary Depression Scale for Schizophrenia (CDSS) score	CDSS is a nine item clinician rated outcome measure that assesses the level of depression in people with schizophrenia. Each item is scored from 0 to 3, higher score indicates more severe symptom.	Baseline, the day of the end of treatment (day 11±1), 1 month after the treatment (day40±7)

Collaborators and Investigators

• Sponsor: Central South University
• Investigators: Study Chair: Renrong Wu, M.D., Ph.D., Mental Health Institute of Second Xiangya Hospital,CSU

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: October 9, 2024
• First Submitted That Met QC Criteria: October 11, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: schizophrenia; TMS; negative symptom
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia
• Other Study ID Numbers: nTMS

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