Psychosis, Schizophrenia
Conditions
Keywords
tDCS, cognitive control, working memory, EEG, gamma oscillations
Brief summary
This study proposes to assess the effect of trans-cranial direct current stimulation (tDCS) on cognitive control, working memory, functional, clinical, and cognitive outcomes in schizophrenia patients.
Detailed description
Cognitive functions and EEG correlates will be thoroughly assessed in schizophrenia patients undergoing a tDCS treatment and compared with patients receiving a placebo stimulation. The treatment will involve 20 minutes of tDCS application to the left prefrontal and temporo-parietal cortex, twice a day for five days, a procedure shown to be effective in improving other symptoms of psychosis such as negative symptoms and hallucinations. Critically, in addition to standard neuropsychological testing, cognitive assessments will involve tasks that tap cognitive control and working memory, impairments in which comprise two of the core cognitive disturbances in schizophrenia and which have been linked to brain rhythm disturbances measurable by EEG recordings. Investigators will also assess changes in functional outcome by tDCS and investigate relationships between improvements in cognition, brain rhythms and functional outcome. All these assessments will occur just prior to tDCS application, just after completion of the tDCS series, and then again at 2 months follow-up. There will be two separate independent groups of patients who will be randomized to active versus sham treatments. The first group will have early course schizophrenia (less than 5 years of antipsychotic treatment; n=40). The second group will be chronic schizophrenia (greater than 5 years of antipsychotic treatment; n=40). Relevance This proposal would be the first integrated study of the effects of tDCS on cognitive symptoms, brain function and functional outcome in schizophrenia. A positive outcome would represent a marked improvement in clinical therapeutics for cognition in psychosis and provide a powerful tool for improving functional outcome in this debilitating disorder. Understanding the impact on brain rhythm disturbances could support the study of similar stimulation-based therapeutic approaches to other neuropsychiatric disorders that shows similar disturbances in cognition and brain rhythms activity, such as bipolar disorder and autism.
Interventions
DEVICEActive Trans-cranial direct-current stimulation
Active stimulation group will receive 20 min of 2 mA direct current stimulation.
DEVICESham Trans-cranial direct current stimulation
This will be an active sham involving brief (15 msec) low current (0.11 mA) pulses every 550 ms.
Sponsors
Brain & Behavior Research Foundation
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
Early course psychosis: * DSM-V diagnosis of Schizophrenia, Schizoaffective disorder, or schizophreniform disorder. * ages 18-50 years * on stable doses of medication for at least one month * not taking benzodiazepines or mood stabilizers. * Mild to severe cognitive impairment in MATRICS Consensus Cognitive Battery (composite scores \< 40) Chronic psychosis: Same as early course psychosis but \>5 years of antipsychotic treatment
Exclusion criteria
* Diagnostic and Statistical Manual-Version V (DSM-V) diagnosis of mental retardation * significant head injury * medical illness affecting brain function or structure * pregnancy or postpartum (\<6 weeks after delivery or miscarriage) * significant neurologic disorder (e.g seizure disorder) * inability to provide informed consent * significant color blindness that affects task performance * Comorbidity for DSM-V substance abuse disorder within the past one month * Temporal relation between illness onset and head injury * Taking benzodiazepines or mood stabilizers (lithium allowed) * Positive drug screen (excluding THC at baseline)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Control | Week 1 | The investigators will assess cognitive control using the Preparing to Overcome Prepotency (POP) task. The accuracy mean differences between the high and low control conditions will be used as dependent measures. The study is powered at 0.8 to observe a post-pre treatment improvement in cognitive control with a substantial effect size (d=0.56) compared to sham stimulation with effects relatively stable measured 2 months after baseline. The hypothesized effect size will be d=0.60. |
| Working Memory | Week 1 | The investigators will assess working memory using a working memory task. The accuracy mean differences between the high and low control conditions will be used as dependent measures. The study is powered at 0.8 to observe a post-pre treatment improvement in cognitive control with a substantial effect size (d=0.56) compared to sham stimulation with effects relatively stable measured 2 months after baseline. The hypothesized effect size will be d=0.60. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Negative Symptoms | Week 1 | A secondary outcome measure is the severity of negative symptoms as quantified by Scale for the Assessment of Negative Symptoms (SANS). This study is powered at 0.8 to observe a post-pre treatment improvement in negative symptoms with a moderate effect size (d=0.56) compared to sham stimulation with effects relatively stable measured 2 months after baseline. The hypothesized effect size will be d=0.60. |
| Auditory Hallucinations | Week 1 | A secondary outcome measure is the change over time in the severity of auditory hallucinations as assessed by the Auditory Hallucination Rating Scale (AHRS). In a study conducted using a similar montage and current strength (Brunelin et. al 2012), a reduction in auditory hallucinations with a substantial effect size (d=1.58) was observed in 30 patients with schizophrenia. However, as their study recruited only those patients with severe hallucinations while the current study does not have such an inclusion criterion. The investigators expect a more modest effect size of d=0.60. |
Countries
United States
Participant flow
Recruitment details
The reason we have fewer subjects randomized than enrolled is that some participants did not meet criteria to be randomized. These subjects were consented and completed many assessments, but were ultimately not randomized due to how they scored on some assessments. For instance, some participants MCCB score was too high to be randomized into the study.
Pre-assignment details
The primary reasons for ineligibility were not taking any anti-psychotic medication, and positive drug screen. There were also many who did not even enter screening due to the assessment that they would highly likely not meet the threshold of requirement cognitive impairment (MATRICS score \< 40).
Participants by arm
| Arm | Count |
|---|---|
| Active Stimulation Active stimulation group will receive 20 min of 2 mA direct current stimulation.
Active Trans-cranial direct-current stimulation: Active stimulation group will receive 20 min of 2 mA direct current stimulation. | 5 |
| Sham Stimulation This will be an active sham involving brief (15 msec) low current (0.11 mA) pulses every 550 ms.
Sham Trans-cranial direct current stimulation: This will be an active sham involving brief (15 msec) low current (0.11 mA) pulses every 550 ms. | 7 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Sham Stimulation | Active Stimulation |
|---|---|---|---|
| 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 | 12 Participants | 7 Participants | 5 Participants |
| Age, Continuous | 33 years STANDARD_DEVIATION 8.3 | 33 years STANDARD_DEVIATION 7.5 | 34 years STANDARD_DEVIATION 10.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 4 Participants | 3 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 | 3 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United States | 12 participants | 7 participants | 5 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 9 Participants | 6 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 7 |
| other Total, other adverse events | 1 / 5 | 1 / 7 |
| serious Total, serious adverse events | 0 / 5 | 0 / 7 |
Outcome results
Primary
Cognitive Control
The investigators will assess cognitive control using the Preparing to Overcome Prepotency (POP) task. The accuracy mean differences between the high and low control conditions will be used as dependent measures. The study is powered at 0.8 to observe a post-pre treatment improvement in cognitive control with a substantial effect size (d=0.56) compared to sham stimulation with effects relatively stable measured 2 months after baseline. The hypothesized effect size will be d=0.60.
Time frame: Week 1
Population: We have reported all available data.
Primary
Working Memory
The investigators will assess working memory using a working memory task. The accuracy mean differences between the high and low control conditions will be used as dependent measures. The study is powered at 0.8 to observe a post-pre treatment improvement in cognitive control with a substantial effect size (d=0.56) compared to sham stimulation with effects relatively stable measured 2 months after baseline. The hypothesized effect size will be d=0.60.
Time frame: Week 1
Population: We have reported all available data.
Secondary
Auditory Hallucinations
A secondary outcome measure is the change over time in the severity of auditory hallucinations as assessed by the Auditory Hallucination Rating Scale (AHRS). In a study conducted using a similar montage and current strength (Brunelin et. al 2012), a reduction in auditory hallucinations with a substantial effect size (d=1.58) was observed in 30 patients with schizophrenia. However, as their study recruited only those patients with severe hallucinations while the current study does not have such an inclusion criterion. The investigators expect a more modest effect size of d=0.60.
Time frame: Week 1
Population: We have reported all available data.
Secondary
Negative Symptoms
A secondary outcome measure is the severity of negative symptoms as quantified by Scale for the Assessment of Negative Symptoms (SANS). This study is powered at 0.8 to observe a post-pre treatment improvement in negative symptoms with a moderate effect size (d=0.56) compared to sham stimulation with effects relatively stable measured 2 months after baseline. The hypothesized effect size will be d=0.60.
Time frame: Week 1
Population: We have reported all available data.