iTBS on Negative Symptoms and Cognitive Function in Schizophrenia

The Effect of Intermittent Theta Burst Stimulation on Negative Symptoms And Cognitive Function in Schizophrenia

The negative symptoms and cognitive deficits are common in patients with schizophrenia, and do not respond well to antipsychotics. The effective treatments for negative symptoms and cognitive impairment are still to be explored. rTMS is a safe and non-invasive physical treatment, some studies has been indicated that the high frequency rTMS could increase the excitability of cortex, and has potentials to improve negative symptoms and cognitive function in schizophrenia. In this study, we explore the effects of iTBS on negative symptoms and cognitive function based on identifying the brain network connection of schizophrenia symptoms.

Study Overview

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

Detailed Description

The negative symptoms and cognitive deficits are two core symptoms in patients with schizophrenia, and do not respond well to antipsychotics. There are many researches on the biological mechanism of these two symptoms, and some studies indicated that these two symptoms maybe related to the dysfunction of prefrontal cortex and deficiency of dopamine. rTMS is a safe and non-invasive physical treatment, some studies has been indicated that the high frequency rTMS could increase the excitability of cortex, and has potentials to improve negative symptoms and cognitive function in schizophrenia.Therefore, this study explore the efficacy of iTBS on negative symptoms and cognitive deficits in schizophrenia based on identifying the brain network connection of schizophrenia symptoms.

Firstly, we have used neuroimaging to find the left prefrontal cortex that is responsible for negative symptoms and cognitive function in schizophrenia. Then,we design this randomized double-blind sham-controlled clinical trial. Patients with schizophrenia will be randomly treated with iTBS or sham condition to the left dorsolateral prefrontal cortex(L-DLPFC) for continuous 10 days, theL-DLPFC will be targeted utilizing the localite neuronavigation system. The follow-ups are set at baseline, the 11th day and the 30th day after the end of treatment. The main outcome measures include the change in MCCB score, PANSS score, SANS score, SAPS score and the resting-state functional magnetic resonance imaging data.

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

Contacts and Locations

• Study Contact: Name: Renrong Wu, Prof; Phone Number: 15874179855; Email: wurenrong@csu.edu.cn

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410000
      • Recruiting
      • Second Xiangya Hospital
      • Contact: Dongyu Kang; Phone Number: 13787142461

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with schizophrenia in accordance with DSM-5
2. The disease duration ≤8 years
3. Received a steady dose of antipsychotic medication for least 4 weeks
4. The Global Deficit Score of MCCB ≥0.5 or the PANSS negative subscore ≥20
5. No obvious extrapyramidal side effects caused by antipsychotic drugs
6. Informed Consent

Exclusion Criteria:

1. Diagnosed with other mental disease in accordance with DSM-5
2. Combined with other severe physiological disease
3. Used antidepressants, mood stabilizer, or other psychoactive substances before
4. Drug or alcohol abuse
5. Pregnant or lactating
6. Contraindication to rTMS
7. Received rTMS or electroconvulsive therapy in the past 1 month

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: iTBS stimulation; The patients in iTBS stimulation group will receive iTBS stimulation on the target of the left dorsolateral prefrontal cortex for 10 consecutive days and 3 times per day.There will have at least 30 minutes interval between each intervention.	Device: Intermittent theta burst stimulation; Intermittent theta burst stimulation(iTBS) on the left DLPFC, the left DLPFC will be targeted utilizing the localite neuronavigation system. The stimulation intensity is set at 80% of resting motor threshold(RMT), and the other parameters are set to triplet 50Hz bursts, repeat at 5Hz, 2s seconds on and 8 seconds off, 600 pulses per session, total duration of 3 minutes and 20 seconds.
Sham Comparator: Sham stimulation; The participants in sham stimulation will receive sham stimulation, as the coil vertical to the brain surface, for 10 consecutive days and 3 times per day.There will have at least 30 minutes interval between each intervention.	Device: Sham stimulation; The same procedure will be performed in sham group including the RMT assessment and the neuronavigation system for target localization, but the sham coil will vertical to the brain surface and deliver a very slight magnetic field, which have the same appearance and sound, and provide the same tactile sensations as the active coils.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in MCCB	The MATRICS Consensus Cognitive Battery,It can be used for cognitive assessment of schizophrenia, bipolar disorder and other neuropsychiatric diseases,The MCCB 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. The working memory domain does not include verbal working memory because the Chinese language would not make feasible the inclusion of the LNS test.	From baseline to 11days and the 30th day after the end of stimulation
Change in Positive and Negative Symptm Scale(PANSS) score	The scale to assess the severity of symptoms in schizophrenia.It is an evaluation scale of 30 disparate items scored from 1 to 7 for psychopathological symptoms observed in patients presenting psychotic syndromes, especially schizophrenic states.Three scores obtained with this scale are generally calculated for evaluating three dimensions of the syndrome: positive, negative and general psychopathology, as part of a categorial or dimensional perspective.The minimum value is 30 points, and the maximum value is 210 points.The higher the score, the more severe the relevant symptom is.	From baseline to 11days and the 30th day after the end of stimulation
Change in Scale for Assessment of Positive Symptoms(SAPS) score	This scale is used to assess the severity of positive symptoms in schizophrenia. Evaluating four dimensions of the positive symptoms including hallucination, delusion, strange behavior and disorders of the positive thinking form.There are 34 items in the scale, which are divided into four subscales and graded on a six-point scale. The total score of the scale is the sum of 34 individual items, reflecting the severity of positive symptoms. The score range is 0-170, the higher the score, the more severe the symptoms are. The total score of the comprehensive evaluation is the sum of the individual score of the overall evaluation item of the four subscales, which also reflects the severity of positive symptoms, the score range is 0-20. The comprehensive evaluation score of the subscale is the single score of the overall evaluation item of the four subscales, specifically reflecting the severity of the four dimensions of the positive symptoms, the score range is 0-5.	From baseline to 11days and the 30th day after the end of stimulation
Change in Scale for Assessment of Negative Symptoms(SANS) score	This scale is used to assess the severity of negative symptoms in schizophrenia. Evaluating five dimensions of the negative symptoms including apathy, poverty of thought, abulia, social withdrawal and disorders of attention.There are 24 items in the scale, which are divided into five subscales and graded on a six-point scale. The total score of the scale is the sum of 24 individual items, reflecting the severity of positive symptoms. The score range is 0-120, the higher the score, the more severe the negative symptoms are. The total score of the comprehensive evaluation is the sum of the individual score of the overall evaluation item of the five subscales, which also reflects the severity of negative symptoms, the score range is 0-25. The comprehensive evaluation score of the subscale is the single score of the overall evaluation item of the five subscales, specifically reflecting the severity of the five dimensions of the negative symptoms, the score range is 0-5.	From baseline to 11days and the 30th day after the end of stimulation
The data of resting-state functional magnetic resonance imaging	All patients undergo head MRI scans in Philips Achieva 3.0 T scanner and SIEMENS Prisma 3.0 T scanner.	From baseline to 11days and the 30th day after the end of stimulation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Treatment Emergent Symptom Scale(TESS) score	The scale is used to assess the side effects of various psychotropic drugs in adult patients. Evaluation is based on patient statements, physical examination and laboratory results.The 34 symptoms were summarized into 6 groups of symptoms, including behavioral adverse reactions, laboratory tests, nervous system reactions, autonomic nervous system symptoms, cardiovascular system reactions and others.The scale evaluation requires a three-pronged assessment of each symptom: severity, the relationship between the symptom and the medication, and the treatment.	From baseline to 11days and the 30th day after the end of stimulation
The blood sample	About 20ml blood samples were collected intravenously to test blood routine, liver and kidney function, electrolytes and other routine tests.	From baseline to 11days and the 30th day after the end of stimulation

Collaborators and Investigators

• Sponsor: Central South University
• Investigators: Principal Investigator: Renrong Wu, Prof, The Second Xiangya Hospital of Central South University Psychiatry Department

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2022
• Primary Completion (Estimated): October 20, 2024
• Study Completion (Estimated): October 20, 2024

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: November 29, 2021
• First Posted (Actual): November 30, 2021

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Schizophrenia; Cognitive function; iTBS; Negative Symptom
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: WU202110TBS

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