rTMS on Mismatch Negativity of Schizophrenia

August 6, 2020 updated by: National Taiwan University Hospital

Using Repetitive Transcranial Magnetic Stimulation to Improve the Auditory Mismatch Negativity Deficits of Schizophrenia: a Randomized, Double-blinded, Sham-controlled Clinical Trial

Auditory mismatch negativity deficit is a robust neurophysiological biomarker of schizophrenia. Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulation method and can be used to modulate excitability of specific brain cortical region. We hypothesize that MMN deficit of schizophrenia is related to inferior frontal gyrus (IFG) hypofunction, and this deficit can be improved by using rTMS to enhance IFG function.

It is a randomized, double-blinded, sham-controlled clinical trial. Forty-eight schizophrenia patients with MMN deficits (mean amplitude at FCz > -0.7 ㎶) will be recruited and then randomized at a 1:1 ratio to rTMS group and sham-stimulation group. Subjects in rTMS group will receive high frequency rTMS over IFG, while in the other group subjects will receive sham stimulation at IFG. Frameless stereotaxy navigation will be used to guide the rTMS coil to IFG. The primary outcome is the change of MMN mean amplitude at FCz after stimulation. We hypothesize that the change of MMN mean amplitude is significantly larger in rTMS group than in sham-stimulation group. Their cognitive function and clinical condition will be evaluated carefully before and after experiments.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

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Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

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48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

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Study Locations

  • Taiwan
      • Taipei, Taiwan, 1002
        • Recruiting
        • Department of Psychiatry, National Taiwan University Hospital
        • Principal Investigator:
          • Yi-Ting Lin, MD
        • Sub-Investigator:
          • Tzung-Jeng Hwang, MD, PhD
        • Sub-Investigator:
          • Cheng-Chung Liu, MD, PhD
        • Contact:
        • Sub-Investigator:
          • Ming H. Hsieh, MD, PhD
        • Sub-Investigator:
          • Chih-Min Liu, MD, PhD
        • Sub-Investigator:
          • Yi-Ling Chien, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision
  • mean amplitude of MMN at FCz greater than -0.7 ㎶
  • moderate or milder disease severity (scoring 4 or below according to clinical global rating scale)

Exclusion Criteria:

  • unwillingness or inability to cooperate with the experiments
  • with mental retardation, epilepsy, or other major brain pathology (e.g. cerebrovascular accidents or major head injury)
  • with alcohol or other illicit substance abuse
  • with major debilitating systemic diseases or difficulties in ambulation
  • with hearing impairments as screened by audiometry over 500 Hz, 1000 Hz and 6000 Hz
  • with pacemaker, intra-ocular metal foreign body, intracerebral vessel clip, artificial cardiac valve, electronic implant in the body, claustrophobia, or previous surgery involving the brain
  • being pregnant or to be pregnant during the clinical trial. A pre-TMS evaluation scale will be applied to ensure the safety

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: rTMS: left first
One-session rTMS is applied to left IFG. Pre-stimulation and post-stimulation MMN is recorded and compared. After at least two weeks, one-session rTMS is applied to right IFG. Pre-stimulation and post-stimulation MMN is recorded and compared as well.
Device: Transcranial magnetic stimulation
For one-session rTMS, 50 trains of stimulation are given. Each train is consisted of 4-second 10 Hz, 100% resting motor threshold TMS pulses. The inter-train interval is 26 seconds.
Experimental: rTMS: right first

One-session rTMS is applied to right IFG. Pre-stimulation and post-stimulation MMN is recorded and compared. After at least two weeks, one-session rTMS is applied to left IFG. Pre-stimulation and post-stimulation MMN is recorded and compared as well.

After at least two weeks, stimulations of the same parameters are given over left IFG. Pre-stimulation and post-stimulation MMN is recorded and compared as well.
Device: Transcranial magnetic stimulation
For one-session rTMS, 50 trains of stimulation are given. Each train is consisted of 4-second 10 Hz, 100% resting motor threshold TMS pulses. The inter-train interval is 26 seconds.
Sham Comparator: Sham: left first
One-session sham stimulation is applied to left IFG. Pre-stimulation and post-stimulation MMN is recorded and compared. After at least two weeks, one-session sham stimulation is applied to right IFG. Pre-stimulation and post-stimulation MMN is recorded and compared as well.
Device: Sham
For one-session sham stimulation, 50 trains of stimulation are given. Each train is consisted of 4-second 10 Hz sham pulses. The inter-train interval is 26 seconds.
Sham Comparator: Sham: right first
One-session sham stimulation is applied to right IFG. Pre-stimulation and post-stimulation MMN is recorded and compared. After at least two weeks, one-session sham stimulation is applied to left IFG. Pre-stimulation and post-stimulation MMN is recorded and compared as well.
Device: Sham
For one-session sham stimulation, 50 trains of stimulation are given. Each train is consisted of 4-second 10 Hz sham pulses. The inter-train interval is 26 seconds.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mismatch negativity (MMN)
Time Frame: 1 day
Mismatch negativity is recorded by electroencephalography and elicited by auditory oddball paradigm in which tone duration deviants are used. MMN is the mean amplitude between 135 and 205 milliseconds after auditory stimuli recorded by electrode FCz.
1 day

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Continuous performance test (CPT)
Time Frame: 1 day
The undegraded 1-9 task and the 25% degraded 1-9 task are used. Sensitivity indices indicating the ability to discriminate target from non-target trials are calculated (d' for undegraded CPT and md' for degraded CPT).
1 day
Wisconsin Card Sorting Test (WCST)
Time Frame: 1 day
Four indices of WCST are derived: perseverative errors, categories achieved, trials to complete first category, and conceptual level response.
1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Taiwan University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 5, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 28, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 28, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 7, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 7, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 9, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 10, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201807026RINB

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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