Schizophrenia
Conditions
Keywords
schizophrenia
Brief summary
1. Exploration of repetitive transcranial magnetic stimulation（rTMS）on working memory and cognitive impairment symptoms of schizophrenia treatment and mechanism. 2. Analysis of high-frequency repetitive transcranial magnetic stimulation stimulation to the improvement of negative symptoms and psychotic symptoms.
Detailed description
The study was a randomized double-blind sham-controlled trial for 4 weeks. Patients with schizophrenia were treated with 20-Hz rTMS for 4 weeks to the left dorsolateral prefrontal cortex (added to the ongoing treatment). Negative symptoms were assessed with the Scale for the Assessment of Negative Symptoms (SANS), the Positive and Negative symptom scale (PANSS).The auditory steady state responses (ASSR) were obtained for the assessment of gamma oscillation.And cognitive symptoms were assessed by MATRICS cognitive test battery (MCCB) Chinese version and n-back task.
Interventions
DEVICERepetitive Transcranial Magnetic Stimulation
The MagPro X100 is connected to a Magnetic Coil which transfers the magnetic stimulation to the tissue. The original coils MC-B65 can be used with the MagPro X100.
Sponsors
Shanghai Mental Health Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 49 Years
Healthy volunteers
No
Inclusion criteria
* 1）patients to be diagnosed according to the Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders(DSM-IV) for paranoid schizophrenia；2）20～49 years old；3）Duration of 2 \ 10 years;4）the disease situation is stable， the fluctuation of Positive and Negative Symptom Scale（PANSS）total score ≤10% in last 1 month, and have accepted the current drugs for more than 8 weeks; 5）Patients, their families and doctors are agreed that the disease situation is stable and maintained current drug treatment in next month；6）Signed an informed consent
Exclusion criteria
* 1)patients to be diagnosed according to DSM-IV for substance abused,development delayed;2)suffering from serious physical disease and can not accept the treatment;3)repetitive transcranial magnetic stimulation(rTMS) contraindications: intracranial metal substance, with heart pacemakers and cochlear implants, intracranial pressure;4)the disease situation is not stable， the fluctuation of Positive and Negative Symptom Scale（PANSS）total score \>10% in last 1 month, Positive and Negative Symptom Scale（PANSS）total score \> 60;5)difficult to maintain the current drug treatment for at least 1 month;6）undergoing electroconvulsive therapy（ECT）in last 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change in the Severity of Negative Symptoms | Baseline, after 4 weeks of treatment | The assessment of negative symptoms were measured with the Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS).The SANS contains 30 particular items divided into 5 symptomatological domains: 1) affective flattening and/or blunting, 2) alogia, 3) avolition and/or apathy, 4) anhedonia, and 5) impaired attention. Each item is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 150. Higher scores indicate more impairment.The PANSS contains 30 particular items divided into 3 subscores: 1)positive, 2) negative, and 3) general subscore. Each item is scored on a scale from 1 (absent) to 7 (extreme) with a total scoring range of 30 to 210. Higher scores indicate more impairment. The primary outcomes were the changes in the severity of negative symptoms as measured with SANS total score and PANSS negative subscore after 4 weeks of intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MATRICS Consensus Cognitive Battery (MCCB) in Chinese Version | Baseline and 4 weeks | MCCB in Chinese Version includes 9 tasks across 7 domains, and a composite score, including Processing Speed (Brief Assessment of Cognition in Schizophrenia Symbol Coding, Animal Fluency, Trails A), Attention (Continuous Performance Test), Working Memory (WMS-III Spatial Span), Verbal Learning (Hopkins Verbal Learning Test - Revised), Visual Learning (Brief Visuospatial Memory Test - Revised), Problem Solving (Neuropsychological Assessment Battery), and Social Cognition (Mayer-Salovey- Caruso Emotional Intelligence Test).The results are reported as T scores with a mean of 50 and an SD of 10. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Event-related Spectral Perturbation (ERSP) | 4 weeks | Alterations in gamma-band ASSR have been thought to be the most robust finding of abnormal neural oscillations in patients with schizophrenia. EEG data were acquired using a 64-electrode cap and alternating current BrainAmp amplifiers (Brain Products GmbH, Germany). We used EEGLAB to perform time-frequency analysis with a short-term Fourier transformation, and then calculated ERSP. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active rTMS Active treatment will be delivered at an intensity that is 80% of the resting motor threshold (RMT). Stimulation will be delivered at 20 Hz with 100 stimulation trains of 20 stimuli each (i.e., 2000 stimuli) and an inter-train interval of 9 sec. Treatment will be applied in sequential order to the left dorsolateral prefrontal cortex (DLPFC). Intervention: Device: Repetitive Transcranial Magnetic Stimulation
Repetitive Transcranial Magnetic Stimulation: The MagPro X100 is connected to a Magnetic Coil which transfers the magnetic stimulation to the tissue. The original coils MC-B65 can be used with the MagPro X100. | 35 |
| Sham rTMS Sham rTMS stimulation will be delivered using the same stimulation parameters and at the site of active treatment, but the coil will be reversed. This method produces sound and some somatic sensation (e.g., contraction of scalp muscles) similar to those of active stimulation, but with minimal direct brain effects.
Repetitive Transcranial Magnetic Stimulation: The MagPro X100 is connected to a Magnetic Coil which transfers the magnetic stimulation to the tissue. The original coils MC-B65 can be used with the MagPro X100. | 35 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 8 |
Baseline characteristics
| Characteristic | Active rTMS | Sham rTMS | 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 | 35 Participants | 35 Participants | 70 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 35 Participants | 35 Participants | 70 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 | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 35 participants | 35 participants | 70 participants |
| Sex: Female, Male Female | 13 Participants | 10 Participants | 23 Participants |
| Sex: Female, Male Male | 22 Participants | 25 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 35 | 5 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 35 |
Outcome results
Primary
The Change in the Severity of Negative Symptoms
The assessment of negative symptoms were measured with the Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS).The SANS contains 30 particular items divided into 5 symptomatological domains: 1) affective flattening and/or blunting, 2) alogia, 3) avolition and/or apathy, 4) anhedonia, and 5) impaired attention. Each item is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 150. Higher scores indicate more impairment.The PANSS contains 30 particular items divided into 3 subscores: 1)positive, 2) negative, and 3) general subscore. Each item is scored on a scale from 1 (absent) to 7 (extreme) with a total scoring range of 30 to 210. Higher scores indicate more impairment. The primary outcomes were the changes in the severity of negative symptoms as measured with SANS total score and PANSS negative subscore after 4 weeks of intervention.
Time frame: Baseline, after 4 weeks of treatment
Population: Ten patients dropped out due to different reasons (three patients refused to participated, three did not complianted and the other four were discharged before completion of study)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Active rTMS | The Change in the Severity of Negative Symptoms | SANS（Baseline） | 48.09 units on a scale |
| Active rTMS | The Change in the Severity of Negative Symptoms | SANS（4 weeks） | 33.91 units on a scale |
| Active rTMS | The Change in the Severity of Negative Symptoms | PANSS（Baseline） | 68.15 units on a scale |
| Active rTMS | The Change in the Severity of Negative Symptoms | PANSS（4 weeks） | 54.58 units on a scale |
| Sham rTMS | The Change in the Severity of Negative Symptoms | PANSS（4 weeks） | 59.85 units on a scale |
| Sham rTMS | The Change in the Severity of Negative Symptoms | SANS（Baseline） | 50.33 units on a scale |
| Sham rTMS | The Change in the Severity of Negative Symptoms | PANSS（Baseline） | 69.93 units on a scale |
| Sham rTMS | The Change in the Severity of Negative Symptoms | SANS（4 weeks） | 41.00 units on a scale |
Secondary
MATRICS Consensus Cognitive Battery (MCCB) in Chinese Version
MCCB in Chinese Version includes 9 tasks across 7 domains, and a composite score, including Processing Speed (Brief Assessment of Cognition in Schizophrenia Symbol Coding, Animal Fluency, Trails A), Attention (Continuous Performance Test), Working Memory (WMS-III Spatial Span), Verbal Learning (Hopkins Verbal Learning Test - Revised), Visual Learning (Brief Visuospatial Memory Test - Revised), Problem Solving (Neuropsychological Assessment Battery), and Social Cognition (Mayer-Salovey- Caruso Emotional Intelligence Test).The results are reported as T scores with a mean of 50 and an SD of 10.
Time frame: Baseline and 4 weeks
Population: Ten patients dropped out due to different reasons (three patients refused to participated, three did not complianted and the other four were discharged before completion of study)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active rTMS | MATRICS Consensus Cognitive Battery (MCCB) in Chinese Version | Composite score (baseline) | 45.07 MCCB(T score) | Standard Deviation 6.48 |
| Active rTMS | MATRICS Consensus Cognitive Battery (MCCB) in Chinese Version | Composite score (4 weeks) | 48.00 MCCB(T score) | Standard Deviation 7.16 |
| Sham rTMS | MATRICS Consensus Cognitive Battery (MCCB) in Chinese Version | Composite score (baseline) | 43.58 MCCB(T score) | Standard Deviation 9.25 |
| Sham rTMS | MATRICS Consensus Cognitive Battery (MCCB) in Chinese Version | Composite score (4 weeks) | 49.04 MCCB(T score) | Standard Deviation 7.46 |
Other Pre-specified
Event-related Spectral Perturbation (ERSP)
Alterations in gamma-band ASSR have been thought to be the most robust finding of abnormal neural oscillations in patients with schizophrenia. EEG data were acquired using a 64-electrode cap and alternating current BrainAmp amplifiers (Brain Products GmbH, Germany). We used EEGLAB to perform time-frequency analysis with a short-term Fourier transformation, and then calculated ERSP.
Time frame: 4 weeks
Population: patients discontinualed treatment
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Active rTMS | Event-related Spectral Perturbation (ERSP) | baseline | 0.365 dB |
| Active rTMS | Event-related Spectral Perturbation (ERSP) | 4 weeks | 0.390 dB |
| Sham rTMS | Event-related Spectral Perturbation (ERSP) | baseline | 0.327 dB |
| Sham rTMS | Event-related Spectral Perturbation (ERSP) | 4 weeks | 0.382 dB |