Optimal rTMS for Cognitive Deficits and Negative Symptoms in Schizophrenia

Optimizing Treatment Protocol of High Frequency Repetitive Transcranial Magnetic Stimulation for Cognitive Deficits and Negative Symptoms in Schizophrenia: an Exploratory Study

Negative symptoms and cognition decline are major challenges in clinical management of schizophrenia. Dorsomedial prefrontal cortex (DLPFC) has been highly involved in the mechanisms of negative symptoms and cognitive symptoms of schizophrenia. However, the effect of repetitive transcranial magnetic stimulation (rTMS) over left or bilateral DLPFC has not yet been well studied. The aim of this study is to describe how the effectiveness of rTMS over different targets for cognitive deficits and negative symptoms in schizophrenia will be evaluated. The study will provide evidence to determine whether a bilateral DLPFC rTMS and is more effective than a left DLPFC rTMS alone to optimize treatment protocol in schizophrenia.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Cognitive Impairment; Repetitive Transcranial Magnetic Stimulation; Negative Symptoms in Schizophrenia; Dorsolateral Prefrontal Cortex
• Intervention / Treatment: Device: Bilateral Active Repetitive transcranial magnetic stimulation (rTMS); Device: Left Active Repetitive transcranial magnetic stimulation (rTMS); Device: Sham rTMS over bilateral dorsolateral prefrontal cortex

Detailed Description

The study will be a randomized, double-blind trial comparing active rTMS over bilateral DLPFC vs. active rTMS over left DLPFC vs. sham rTMS delivered over DLPFC an 4-week treatment period. After assessment and inclusion into the study, participants will be randomized to receive up to 20 sessions of either active rTMS over left DLPFC or bilateral DLPFC or placebo treatments.

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

Contacts and Locations

• Study Contact: Name: Yan Zhan, MD; Phone Number: 18917757626; Email: [email protected]
• Study Contact Backup: Name: Suzhen Zhang, MD; Phone Number: 18257209627; Email: [email protected]

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 20030
      • Recruiting
      • Shanghai Xuhui Mental Health Center
      • Contact: Yan Zhan, MD; Phone Number: 18917757626; Email: [email protected]

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 59 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Met the Diagnostic and Statistical Manual of Mental Disorders, Five Edition (DSM-V) diagnostic criteria for schizophrenia and the diagnosis was verified by an experienced psychiatrist based on the Mini-International Neuropsychiatric Interview (MINI) 7.0 .
• Age between 18 and 60.
• Patients with prominently negative symptoms, which was defined as: PANSS negative subscore≥15 points and one of items N1-N7 scoring≥4.
• All patients were in stable clinical conditions (reduction rate of PANSS score<10% within 4 weeks), stable antipsychotic treatment for at least 4 weeks, and able to provide informed consent.

Exclusion Criteria:

• Any contraindication for rTMS (e.g., intracranial metal, pacemakers, cochlear and intracranial hypertension).
• Unstable clinical condition (e.g., being aggressive and uncooperative).
• Current substance abuse.
• Any other psychiatric diagnosis.
• Significant medical condition including neurological disease, severe cardiovascular, hepatic, renal diseases.
• Previous treatment with modified electric convulsive therapy (MECT) within 3 months before enrollment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active rTMS over bilateral dorsolateral prefrontal cortex; Active rTMS over bilateral dorsolateral prefrontal cortex. Participants will receive up to 20 rTMS sessions within the 4-week treatment period.	Device: Bilateral Active Repetitive transcranial magnetic stimulation (rTMS); Active treatments with repetitive transcranial magnetic stimulation (rTMS) over bilateral dorsolateral prefrontal cortex (DLPFC) took the form of intermittent theta burst stimulation (iTBS). For iTBS the stimulation parameters were: frequency = triplet 50 Hz bursts, repeated at 5 Hz; train duration = 2 s ON and 8 s OFF, total pulses/session = 600; total number of treatments = 20(5 sessions per week) at 80 % of each side resting motor threshold (MT). The rTMS target was first randomized to the left or right DLPFC, then switched to the opposite side.
Active Comparator: Active rTMS over left dorsolateral prefrontal cortex; Active rTMS over left dorsolateral prefrontal cortex and sham rTMS over right dorsolateral prefrontal cortex. Participants will receive up to 20 rTMS sessions within the 4-week treatment period.	Device: Left Active Repetitive transcranial magnetic stimulation (rTMS); Active treatments with repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex(DLPFC) took the form of intermittent theta burst stimulation (iTBS). For iTBS the stimulation parameters were: frequency = triplet 50 Hz bursts, repeated at 5 Hz; train duration = 2 s ON and 8 s OFF, total pulses/session = 600; total number of treatments = 20(5 sessions per week) at 80 % of left resting motor threshold (MT). Sham rTMS stimulation was delivered over right dorsolateral prefrontal cortex(DLPFC) using the same stimulation parameters, except for using the sham stimulation coil. The rTMS target was first randomized to the left or right DLPFC, then switched to the opposite side.
Sham Comparator: Sham rTMS over bilateral dorsolateral prefrontal cortex; Sham rTMS over bilateral dorsolateral prefrontal cortex. Participants will receive up to 20 rTMS sessions within the 4-week treatment period.	Device: Sham rTMS over bilateral dorsolateral prefrontal cortex; Sham rTMS stimulation was delivered over bilateral dorsolateral prefrontal cortex (DLPFC) using the same stimulation parameters, except for using the sham stimulation coil. The rTMS target was first randomized to the left or right DLPFC, then switched to the opposite side.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Assessment of Negative Symptoms(SANS) Post Treatment	The Assessment of Negative Symptoms(SANS) is a standardized assessment utilizing a 6-point scale with which the clinician rates the degree to which the severity of the subject's negative symptoms. It consists of 19 items assessing five symptoms of the negative dimension: Affect flattening, alogia, avolition-apathy, anhedonia-asociality, and poor attention.	Baseline and 4 weeks
Mean Change From Baseline in MATRICS Consensus Cognitive Battery Post Treatment	The MATRICS Consensus Cognitive Batteryis a standardized rating tool to assess the severity of the subject's cognitive symptoms, which consisted of seven domains and the total score: speed of processing, attention/vigilance, working memory, visual learning, verbal learning, reasoning/problem solving, and social cognition.	Baseline and 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Positive and Negative Syndrome Scale(PANSS)-Negative Symptoms Subscale Post Treatment	The Positive and Negative Syndrome Scale(PANSS)-Negative Subscale is a valid assessment utilizing a 7 items, 7-point scale with which the clinician rates the degree to which the severity of the subject's negative symptoms.	Baseline and 4 weeks
Mean Change From Baseline in Clinical Global Impression - Severity (CGI-S) Post Treatment	The Clinical Global Impression - Severity (CGI-S) is a standardized assessment utilizing a single item, 7-point scale with which the clinician rates the severity of the subject's illness at the time of assessment relative to the clinician's past experience with patients who have the same diagnosis.	Baseline and 4 weeks
Mean Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Post Treatment	Calgary Depression Scale for Schizophrenia (CDSS) is a nine item structures interview scale, in which each item has a four point measure, which has been specifically developed to assess depression in schizophrenics.	Baseline and 4 weeks

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Collaborators: Xuhui Mental Health Center
• Investigators: Principal Investigator: Yan Zhan, MD, Shanghai Xuhui Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: October 9, 2022
• First Submitted That Met QC Criteria: October 25, 2022
• First Posted (Actual): October 31, 2022

Study Record Updates

• Last Update Posted (Actual): October 31, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Cognitive Dysfunction; Cognition Disorders
• Other Study ID Numbers: XHJW2020KY003

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