Schizoaffective Disorder, Schizophrenia
Conditions
Keywords
Schizophrenia, Transcranial magnetic stimulation, Electroencephalography
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.
Interventions
DEVICERepetitive 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.
DEVICESham
Subjects will still attend treatment sessions as outlined in the rTMS intervention. However, the device will not deliver any stimulation to the subject.
Sponsors
Stanford University
University of South Carolina
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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%. |
| 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 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 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. |
Countries
United States
Participant flow
Recruitment details
Of the approached potential participants, many were unable to participate due to difficulties with the amount of time required to participate in the study, or a change in interest.
Participants by arm
| Arm | Count |
|---|---|
| Active Subjects will receive actual rTMS treatment.
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. | 5 |
| Sham Subjects will attend and sit through the session, but no rTMS treatment will be actually delivered to them.
Sham: Subjects will still attend treatment sessions as outlined in the rTMS intervention. However, the device will not deliver any stimulation to the subject. | 4 |
| Total | 9 |
Baseline characteristics
| Characteristic | Active | Sham | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 4 Participants | 9 Participants |
| Age, Continuous | 49.2 years STANDARD_DEVIATION 10.2 | 40.5 years STANDARD_DEVIATION 14.5 | 45.3 years STANDARD_DEVIATION 12.6 |
| Brief Assessment of Cognition in Schizophrenia (BACS) Composite T-score Score at Baseline | 33.75 T-score STANDARD_DEVIATION 10.1 | 33.5 T-score STANDARD_DEVIATION 10.66 | 33.62 T-score STANDARD_DEVIATION 10.56 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 3 Participants | 8 Participants |
| Region of Enrollment United States | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 |
| other Total, other adverse events | 0 / 5 | 0 / 4 |
| serious Total, serious adverse events | 1 / 5 | 0 / 4 |
Outcome results
Primary
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.
Time frame: before treatment and after 6-week treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in General Cognitive Ability | -.104 Z-score | Standard Deviation 0.216 |
| Sham | Change in General Cognitive Ability | .505 Z-score | Standard Deviation 0.374 |
Primary
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.
Time frame: before treatment and after 6-week treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in Level of Everyday Functioning | 0 score on a scale | Standard Deviation 3.1 |
| Sham | Change in Level of Everyday Functioning | -.5 score on a scale | Standard Deviation 1.7 |
p-value: 0.782t-test, 2 sided
Primary
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.
Time frame: before treatment and after 6-week treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in Neurophysiologic Function | 0 wavelet coefficient in dB | Standard Deviation 0.025 |
| Sham | Change in Neurophysiologic Function | 0 wavelet coefficient in dB | Standard Deviation 0.03 |
Primary
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%.
Time frame: before treatment and after 6-week treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in Working Memory Function | -7.28 % change in Working Memory Task Accuracy | Standard Deviation 12.95577091 |
| Sham | Change in Working Memory Function | -5.9 % change in Working Memory Task Accuracy | Standard Deviation 15.55040192 |
p-value: 0.849t-test, 2 sided