Improving Neurocognitive Deficits and Function in Schizophrenia With Transcranial Magnetic Stimulation

Not Applicable

Completed

Conditions: Schizoaffective Disorder
Schizophrenia

Interventions: Device: Sham
Device: Repetitive transcranial magnetic stimulation

Registration Number: NCT03037983

Lead Sponsor: VA Office of Research and Development

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 9

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham rTMS	Sham	Subjects will attend and sit through the session, but no rTMS treatment will be actually delivered to them.
Active rTMS	Repetitive transcranial magnetic stimulation	Subjects will receive actual rTMS treatment.

Primary Outcome Measures

Name	Time	Method
Change in Level of Everyday Functioning	before treatment and after 6-week treatment	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.
Change in Neurophysiologic Function	before treatment and after 6-week treatment	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.
Change in General Cognitive Ability	before treatment and after 6-week treatment	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.
Change in Working Memory Function	before treatment and after 6-week treatment	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%.