Schizophrenia
Conditions
Keywords
Schizophrenia
Brief summary
The purpose of the present research is to test a potential new treatment for auditory verbal hallucinations in schizophrenia that uses transcranial Direct Current Stimulation (tDCS), a neurostimulation technique that passes an extremely weak electric current through the brain. During the treatment, two electrodes are positioned on the scalp above regions of the brain implicated in abnormal cortical activity associated with auditory verbal hallucinations in schizophrenia. Due to the directional flow of current, one electrode, termed cathodal,inhibits cortical activity, and the other, termed anodal, increases cortical activity. These electrodes will be placed such that cathodal stimulation is applied to an area associated with hyperactivity and anodal stimulation to an area associated with hypoactivity. One preliminary study has revealed that this form of neurostimulation can alleviate auditory verbal hallucination symptoms both immediately following five days of treatment and up to three months after the final treatment. The goal of this study is to replicate these effects and explore the mechanisms that may underpin them.
Detailed description
90 patients with persistent auditory verbal hallucinations will be recruited to this study. Each individual will participate in behavioral assessments lasting up to 3 hours each and will then be randomized to receive a series of active vs. sham tDCS treatments. For active treatment, patients will have the inhibitory (cathodal) tDCS electrode placed over left auditory cortex relative to an anodal placed over frontal cortex on the right side. tDCS treatments will take place for 20 min per day for 5 consecutive days. For sham, procedures will be similar except that sham (inactive) tDCS treatment will be used. Assessment batteries will then be repeated following completion of treatment and at 1 and 3 mo following treatment. In addition, patients will be offered the possibility to participate in a concurrent magnetic resonance imaging (MRI) study aimed at evaluating the effects of tDCS on activation of auditory cortex during an auditory discrimination task as well as on other imaging parameters related to resting brain activity and metabolism. Patients who agree to participate in this MRI study will be scanned before and after active or sham tDCS. In addition, 5-15 schizophrenia patients will complete a week of High-density, e.g., high-definition tDCS (HD-tDCS) open label. In addition to hallucinating patients, we will recruit up to 20 healthy controls and 20 non-hallucinating patients, who will have similar assessments to the patients, but will not receive tDCS. Overall, the investigators hypothesize that tDCS treatment will lead to reduction in hallucinations, improvement in auditory function, and change in EEG and MRI measurements so that patients more closely resemble healthy volunteers and non-hallucinating patients.
Interventions
DEVICEtranscranial Direct Current Stimulation (tDCS)
A neurostimulation technique that passes an extremely weak electric current through the brain.
DEVICESham tDCS
Sham (inactive) tDCS treatment
Sponsors
Stanley Medical Research Institute
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Age between 18-55 * Structured Clinical Interview for DSM Disorders (SCID) primary diagnosis of DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-Version IV) schizophrenia or schizoaffective disorder * Persistent auditory verbal hallucinations * Right handed * Stable antipsychotic medication for \> 4 weeks * Normal hearing * If female and not infertile, must agree to use one of the following forms of contraception for the duration of study participation: systemic hormonal treatment, an interuterine device (IUD) which was implanted at least 2 months prior to screening, or double-barrier contraception * Willing/capacity to provide informed consent
Exclusion criteria
* Substance dependence or abuse (excluding nicotine) in the past 90 days * Current significant laboratory abnormality * History of seizure, epilepsy in self or fist degree relatives, stroke, brain surgery, head injury with loss of consciousness \> 1 hour or clear cognitive sequelae, intracranial metal implants, known structural brain lesion, devices that may be affected by transcranial Direct Current Stimulation (tDCS) (pacemaker, medication pump, cochlear implant, implanted brain stimulator) * Frequent and persistent migraines * History of adverse reaction to neurostimulation or open skin wounds that would preclude safe placement of tDCS electrodes * Participation in study of investigational medication/device within 4 weeks * Current use of medications known to lower seizure threshold (lithium, serotonergic or tricyclic antidepressants) * If female, pregnant or breast feeding at the time of screening * For MRI study only: Claustrophobia or metal implants or paramagnetic objects contained within the body which may interfere with the MRI scan, as determined according to the guidelines set forth in the following reference book: Guide to MR procedures and metallic objects Shellock, PhD, Lippincott-Raven press, NY 1998
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severity of Refractory Auditory Hallucinations | Auditory Hallucination Rating Scale score after one month | Total score: Auditory hallucinations as determined by Auditory Hallucinations Rating Scale (AHRS). This is a seven item scale rating auditory hallucinations. Total score ranges from 1 to 41, with higher scores more severe. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Transcranial Direct Current Stimulation Transcranial Direct Current Stimulation (tDCS) treatments will take place for 20 minutes per day for 5 consecutive days
transcranial Direct Current Stimulation (tDCS): A neurostimulation technique that passes an extremely weak electric current through the brain. | 47 |
| Sham tDCS Sham tDCS(inactive)treatment (transcranial Direct Current Stimulation) will take place for 20 minutes per day for 5 consecutive days.
Sham tDCS: Sham (inactive) tDCS treatment | 42 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Post Treatment (One Month) | Lost to Follow-up | 3 | 4 |
Baseline characteristics
| Characteristic | Transcranial Direct Current Stimulation | Sham tDCS | Total |
|---|---|---|---|
| Age, Continuous | 38.2 years STANDARD_DEVIATION 9.9 | 40.1 years STANDARD_DEVIATION 8.6 | 39.1 years STANDARD_DEVIATION 9.3 |
| Auditory Hallucination Rating Scale (AHRS) total score | 24.8 units on a scale (total score) STANDARD_DEVIATION 5.7 | 25.2 units on a scale (total score) STANDARD_DEVIATION 5.7 | 25.0 units on a scale (total score) STANDARD_DEVIATION 5.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 8 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 34 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 15 Participants | 7 Participants | 22 Participants |
| Sex: Female, Male Male | 32 Participants | 35 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 42 |
| other Total, other adverse events | 0 / 47 | 0 / 42 |
| serious Total, serious adverse events | 0 / 47 | 0 / 42 |
Outcome results
Primary
Severity of Refractory Auditory Hallucinations
Total score: Auditory hallucinations as determined by Auditory Hallucinations Rating Scale (AHRS). This is a seven item scale rating auditory hallucinations. Total score ranges from 1 to 41, with higher scores more severe.
Time frame: Auditory Hallucination Rating Scale score after one month
Population: Population at one month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Transcranial Direct Current Stimulation | Severity of Refractory Auditory Hallucinations | 20.1 AHRS total score | Standard Deviation 9.9 |
| Sham tDCS | Severity of Refractory Auditory Hallucinations | 23.1 AHRS total score | Standard Deviation 6.8 |
p-value: 0.036ANCOVA