Improving Neurocognitive Deficits and Function in Schizophrenia With Transcranial Magnetic Stimulation

The purpose of this study is to determine whether repetitive transcranial magnetic stimulation (rTMS) is effective in remediating cognitive deficits while also improving functionality in Veterans with schizophrenia.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder
• Intervention / Treatment: Device: Repetitive transcranial magnetic stimulation; Device: Sham

Detailed Description

High-frequency, repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC), the dysfunctional brain region most implicated in cognitive deficits in schizophrenia, has recently been shown to improve cognition in non-Veteran samples with schizophrenia. The investigators' goal is to confirm the efficacy of this treatment modality to remediate cognitive deficits and improve functionality in Veterans with schizophrenia, as well as to gain a better understanding of the neural mechanisms responsible for cognitive deficits and their remediation. The investigators propose conducting a small-scale study to generate pilot data supporting the feasibility of conducting rTMS with Veterans and the effectiveness of rTMS in this population. In addition, the investigators will conduct neurophysiologic experiments to test whether certain neural maker of abnormal brain function improves with rTMS.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304-1207
      • VA Palo Alto Health Care System, Palo Alto, CA

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• SCID (Structured Clinical Interview for DSM Disorders) confirmed diagnosis of Schizophrenia or Schizoaffective Disorder
• Stable medication regimen (no change in dose or agents within the 2 weeks prior to study entry and throughout the duration of the study)
• Stable social environment and housing to enable regular attendance at clinic visits
• Ability to undergo cognitive testing, EEG scans and rTMS
• IQ (intelligence quotient) > 80 (WASI full scale score)
• In general good medical health
• Is in treatment with a psychiatrist and/or primary care physician within the VHA (Veteran's Health Administration) system

Exclusion Criteria:

• Pregnant or lactating female
• History of prior adverse reaction to TMS

• On medications known to significantly lower seizure threshold, e.g.:

  • clozapine
  • chlorpromazine
  • clomipramine
• History of seizures or conditions known to substantially increase risk for seizures
• Implants or medical devices incompatible with TMS

• Acute or unstable chronic illness that would affect participation or compliance with study procedures, e.g.:

  • unstable angina
• Substance abuse/dependence (not including caffeine or nicotine) within one-month period prior to study entry or during study participation

• Unstable psychiatric symptoms that precludes consistent participation in the study, e.g.:

  • active current suicidal intent or plan
  • severe psychosis
• History of loss of consciousness greater than 15 minutes due to head injury.
• Participation in another concurrent clinical trial
• Patients with prior exposure to rTMS
• Have a mass lesion, cerebral infarct or other active central nervous system disease, or history of traumatic brain injury

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active rTMS; Subjects will receive actual rTMS treatment.	Device: Repetitive transcranial magnetic stimulation; rTMS is a non-invasive procedure, in which the administration of a transient magnetic field induces electrical currents in specific, targeted brain regions. The intervention will be administered in 20 sessions lasting 50 minutes each over the course of 2-6 weeks. Up to two sessions may be scheduled per day with a one-hour interval in-between.; Other Names: rTMS
Sham Comparator: Sham rTMS; Subjects will attend and sit through the session, but no rTMS treatment will be actually delivered to them.	Device: Sham; Subjects will still attend treatment sessions as outlined in the rTMS intervention. However, the device will not deliver any stimulation to the subject.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Working Memory Function	Changes in scores for working memory performance accuracy will serve as dependent measure for testing the hypothesis that rTMS improves working memory. Working memory performance was assessed using a non-standardized task developed in house, which is basically a Sterberg style delayed response task in which memoranda are displayed and are to be remembered across a short delay period. The hypothesis will be supported if the investigators find greater working memory difference in the active compared to the sham-rTMS-treated groups as revealed by t-tests and two-sided tests at an alpha level of 0.05. Scores will be reported as a change in percent accuracy during this working memory task, where higher percent accuracy is better and scores range from -100% to 100%.	before treatment and after 6-week treatment
Change in Neurophysiologic Function	Gamma oscillation is viewed as a measure of neurophysiologic function. The investigators will be conducting task-evoked electroencephalography (EEG) to measure gamma oscillation before and after rTMS. It is predicted that the intervention will improve gamma oscillations.	before treatment and after 6-week treatment
Change in Level of Everyday Functioning	Changes in Global Functioning Scale scores (GF) will serve as dependent measure for testing the hypothesis that rTMS improves functioning. The hypothesis will be supported if the investigators find greater GF-difference in the active compared to the sham-rTMS-treated groups as revealed by t-tests and two-sided tests at an alpha level of 0.05. Scale's values range from a minimum score of 1 to a maximum score of 10, with a higher score means better functioning.	before treatment and after 6-week treatment
Change in General Cognitive Ability	Changes in Brief Assessment of Cognition (BACS) score will serve as a dependent measure for testing the hypothesis that rTMS improves cognitive functioning. The hypothesis will be supported if the investigators find greater GF-difference in the active compared to the sham-rTMS-treated groups as revealed by t-tests and two-sided tests at an alpha level of 0.05. Data will be reported as change in Z-score on the scale, where a higher value means a better outcome, with scores ranging from -3 to 3.	before treatment and after 6-week treatment

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Stanford University; University of South Carolina
• Investigators: Principal Investigator: Jong H. Yoon, MD, VA Palo Alto Health Care System, Palo Alto, CA

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): July 18, 2019
• Study Completion (Actual): July 18, 2019

Study Registration Dates

• First Submitted: January 27, 2017
• First Submitted That Met QC Criteria: January 27, 2017
• First Posted (Estimated): January 31, 2017

Study Record Updates

• Last Update Posted (Actual): August 15, 2024
• Last Update Submitted That Met QC Criteria: August 13, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Schizophrenia; Transcranial magnetic stimulation; Electroencephalography
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders
• Other Study ID Numbers: D2382-P; 12246865 (Other Grant/Funding Number: Veterans Affairs - Rehabilitation R&D); 38101 (Other Identifier: Stanford IRB)

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