SCHIZOPHRENIA 1 (Disorder)
Conditions
Keywords
schizophrenia, TMS, repetitive transcranial magnetic stimulation, rTMS, TBS
Brief summary
This randomized controlled trial (RCT) is the first to evaluate the efficacy and safety of a multi-target TMS protocol targeting the right orbitofrontal cortex (R-OFC), left dorsolateral prefrontal cortex (L-DLPFC), and left inferior parietal lobule (L-IPL) for negative symptoms of schizophrenia.
Detailed description
Schizophrenia is a chronic and severe mental disorder. Although antipsychotic medications are effective for positive symptoms, they offer limited improvement for negative symptoms and cognitive deficits. Effective treatments for these symptoms are still lacking. To address current clinical bottlenecks, there is an urgent need to develop novel, effective treatment strategies. Repetitive transcranial magnetic stimulation (rTMS) is a recently developed neuromodulation technique. The latest evidence-based guidelines indicate that the level of evidence for rTMS in treating schizophrenia remains low (i.e., Level C evidence, possibly effective). However, the critical parameter of target selection has not received sufficient attention. This randomized controlled trial (RCT) is the first to evaluate the efficacy and safety of a multi-target TMS protocol targeting the Right Orbitofrontal Cortex (R-OFC), Left Dorsolateral Prefrontal Cortex (L-DLPFC), and Left Inferior Parietal Lobe (L-IPL) for negative symptoms of schizophrenia. MRI-guided neuronavigation will be used to localize targets in each subject. The intensity of TMS stimulations is set to 80-120% of resting motor threshold (RMT). A total of 50 TMS sessions will be administered. The stimulation sequence will be R-OFC (1 Hz) → L-DLPFC (iTBS) → L-IPL (iTBS). The first target (R-OFC) will receive 720 pulses at 1 Hz, while the second and third targets (L-DLPFC and L-IPL) will each receive 900 pulses of iTBS. Five sessions will be delivered per day for 10 consecutive working days, with a 60-minute interval between sessions. Clinical assessments, cognitive evaluations, and resting-state functional Magnetic Resonance Imaging (MRI) scans will be performed before and after TMS treatment.
Interventions
DEVICErepetitive transcranial magnetic stimulation (rTMS)
Repetitive transcranial magnetic stimulation (rTMS) is a recently developed neuromodulation technique.
Sponsors
Shanghai Mental Health Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Outpatients or inpatients at the Department of Psychiatry, Shanghai Mental Health Center; 2. Meet the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for first-episode schizophrenia (diagnosed using the Structured Clinical Interview for DSM-5, SCID-5); disease duration less than 5 years at enrollment; 3. Male or female aged 16-45 years; 4. Education duration ≥ 9 years; 5. Stable medication regimen for at least 6 weeks prior to baseline visit and throughout the study period; psychiatric symptoms generally stable within 1 month prior to baseline visit; 6. Participants and their guardians can understand and sign written informed consent; 7. Total score on the PANSS Negative Symptom subscale (PANSS-N) \> 15, and at least one item score ≥ 3.
Exclusion criteria
1. Current or lifetime psychiatric disorders as determined by SCID-5 assessment; 2. Severe or unstable physical illnesses, including: neurological disorders (delirium, dementia, stroke, epilepsy, migraine, etc.), congestive heart failure, angina pectoris, myocardial infarction, arrhythmia, hypertension, hyperglycemia, malignant tumors, and immunocompromised conditions; 3. Alcohol abuse within 30 days prior to the study or alcohol/drug dependence within 6 months prior to the study; participation in any clinical trial within 30 days prior to baseline; 4. Pregnant or breastfeeding women; 5. Intellectual disability (IQ \< 70); 6. No history of modified electroconvulsive therapy (mECT) within the past 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in severity of negative symptoms before and after TMS intervention, i.e., change in Positive and Negative Syndrome Scale - Negative subscale (PANSS-N) | Negative symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and at 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TMS treatment. | Schizophrenia negative symptoms assessed using Positive and Negative Syndrome Scale - Negative subscale (PANSS-N) Minimum value: 7 (each of the 7 items scored 1 = absent) Maximum value: 49 (each of the 7 items scored 7 = extreme) Higher score indicates: Worse outcome (greater severity of negative symptoms) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in cognitive function scores before and after intervention | MATRICS Consensus Cognitive Battery (MCCB) will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and 4 weeks ( Day 42) after completion of TMS treatment. | MATRICS Consensus Cognitive Battery (MCCB) total score and subtest scores |
| Change in positive symptom scores before and after intervention | Positive symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and at 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TMS treatment. | Positive and Negative Syndrome Scale - Positive subscale (PANSS-P) Minimum value: 7 (each of the 7 items scored 1 = absent) Maximum value: 49 (each of the 7 items scored 7 = extreme) Higher score indicates: Worse outcome (greater severity of positive symptoms) |
| Change in general symptom scores before and after intervention | General symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and at 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TMS treatment. | Global Assessment of Functioning (GAF) score. The score ranges from 0 to 100 points. Higher scores indicate better levels of functioning. |
| Change in anxiety symptoms before and after intervention | Anxiety symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and at 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TMS treatment. | Anxiety symptoms measured using Hamilton Anxiety Rating Scale (HAMA). Each item scored 0 (not present) to 4 (severe), total score range 0-56. Higher scores indicate more severe symptoms. |
| Depressive symptoms changes | Depressive symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and at 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TMS treatment. | Depressive symptoms measured using Hamilton Depression Rating Scale (HAMD). Measure of depression severity - total score ranges from 0 (no depression) to 76 (most severe depression) |
| Safety as measured by number of participants with Adverse Events | Record the adverse events reported on that day after completing the day's TMS treatment. This should be done every day during the treatment period (Day 0 - Day 14) | Number of Adverse Events reported during TMS treatment |
| Resting-state functional MRI (rsfMRI) scan | Resting-state functional MRI will be measured at baseline (Day-4±2), and immediately after the 50th session of TMS (Day 14). | Functional MRI scan will be conducted before and after treatment to assess treatment-induced changes in brain connectivity |
Countries
China
Contacts
CONTACTHuiru Cui, Ph.D
Outcome results
None listed