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The planned randomized, sham-controlled, double-blind, monocentric study aims to evaluate the effectiveness of intermittent Theta-Burst Stimulation (iTBS) on negative symptoms and cognitive deficits in schizophrenia. Both the cerebellar vermis and the left dorsolateral prefrontal cortex will be stimulated successively within the same session.
The goal of this trial is to learn if intermittent theta-burst stimulation (iTBS) of the cerebellum and the left dorsolateral prefrontal cortext (DLPFC) can treat negative symptoms and improve cognition in patients with schizophrenia. The main question it aims to answer is:
Does iTBS of the cerebellum and the left DLPFC improve negative symptoms in patients with schizophrenia? Researchers will compare iTBS to sham stimulation to see if iTBS improves negative symptoms.
Participants will:
The study thus seeks to determine whether iTBS of the fronto-cerebellar network might improve negative symptoms and cognition by altering the network's functional activity. Additionally, it will investigate whether a pro-inflammatory cytokine profile could affect iTBS outcomes and whether inflammatory markers could be affected by iTBS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| iTBS | Experimental | Active intermittent theta-burst stimulation of the cerebellar vermis and the left dorsolateral prefrontal cortex |
|
| Sham iTBS | Sham Comparator | Sham intermittent theta-burst stimulation of the cerebellar vermis and the left dorsolateral prefrontal cortex |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intermittent theta-burst stimulation | Device | Intermittent theta-burst stimulation, applied sequentially to the cerebellar vermis and the left dorsolateral prefrontal cortex |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in negative symptoms | Change in negative symptoms, measured with the Clinical Assessment Interview for Negative Symptoms (CAINS). Higher CAINS scores correspond to more negative symptoms. The minimum total score is 0 points, the maximum total score is 52 points. | From enrollment to the end of iTBS treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Change in negative symptoms at 4-week follow-up | Change in negative symptoms, measured with the Clinical Assessment Interview for Negative Symptoms (CAINS). Higher CAINS scores correspond to more negative symptoms. The minimum total score is 0 points, the maximum total score is 52 points. | From enrollment to follow-up 4 weeks after the end of iTBS treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rasmus Schülke, MD (Dr. med.) | Contact | +49 511 532 2039 | schuelke.rasmus@mh-hannover.de |
| Name | Affiliation | Role |
|---|---|---|
| Rasmus Schülke, MD (Dr. med.) | Hannover Medical School | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hannover Medical School | Recruiting | Hanover | Lower Saxony | 30625 | Germany |
Whether IPD may be shared has not yet been decided. IPD might not be shared due to data protection laws.
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| Sham intermittent theta-burst stimulation | Device | Sham intermittent theta-burst stimulation, applied sequentially to the cerebellar vermis and the left dorsolateral prefrontal cortex |
|
| Speech-gesture rating task | Accuracy and speed of evaluations in the Speech-Gesture Rating Task. | From enrollment to the end of iTBS treatment |
| Speech-gesture rating task at 4-week follow-up | Accuracy and speed of evaluations in the Speech-Gesture Rating Task at 4-week follow-up. | From enrollment to follow-up 4 weeks after the end of iTBS treatment |
| Eye-Tracking Task | Changes in eye movements in the Eye-Tracking Task. | From enrollment to the end of iTBS treatment |
| Eye-Tracking Task at 4-week follow-up | Changes in eye movements in the Eye-Tracking Task at 4-week follow-up. | From enrollment to 4 weeks after the end of iTBS treatment |
| Reading the Mind in the Eyes Test | Reading the Mind in the Eyes Test. | From enrollment to 4 weeks after the end of iTBS treatment |
| Reading the Mind in the Eyes Test at 4-week follow-up | Reading the Mind in the Eyes Test at 4-week follow-up. | From enrollment to 4 weeks after the end of iTBS treatment |
| N-Back Test | Working memory performance in the N-Back Test (sensitivity index). | From enrollment to the end of iTBS treatment |
| N-Back Test at 4-week follow-up | Working memory performance in the N-Back Test (sensitivity index) 4 weeks after the end of iTBS treatment. | From enrollment to the end of iTBS treatment |
| FMRI: Resting-state functional connectivity | Changes in resting-state functional connectivity in functional magnetic resonance imaging. Focus on connectivity between cerebellar vermis and DLPFC. | From enrollment to the end of iTBS treatment |
| FMRI: Resting-state functional connectivity at 4-week follow-up | Changes in resting-state functional connectivity in functional magnetic resonance imaging. Focus on connectivity between cerebellar vermis and DLPFC. | From enrollment to 4 weeks after the end of iTBS treatment |
| FMRI: Task-related functional connectivity | Changes in task-related functional connectivity in functional magnetic resonance imaging, for the N-Back-task and the speech-gesture rating task. | From enrollment to the end of iTBS treatment |
| FMRI: Task-related functional connectivity at 4-week follow-up | Changes in task-related functional connectivity in functional magnetic resonance imaging, for the N-Back-task and the speech-gesture rating task. | From enrollment to 4 weeks after the end of iTBS treatment |
| Inflammatory cytokines | Concentrations of inflammatory cytokines (especially IL-6 and TNF-α) in serum and saliva. | From enrollment to the end of iTBS treatment |
| Inflammatory cytokines at 4-week follow-up | Concentrations of inflammatory cytokines (especially IL-6 and TNF-α) in serum and saliva. | From enrollment to 4 weeks after the end of iTBS treatment |
| Stimulation-associated perceptions | Stimulation-associated perceptions, measured using the TMS Adverse Events and Associated Sensations Questionnaire (TMSensQ, Section IV), after each iTBS session. | From the beginning of each iTBS stimulation to after the end of each iTBS stimulation |
| Therapy dropout rate | Therapy dropout rate (i.e. study termination). | From the beginning of iTBS treatment to the end of iTBS treatment |
| Serious Adverse Events (SAEs) | Serious Adverse Events (SAEs), measured using TMSensQ (Section V). | From the beginning of iTBS treatment to the end of iTBS treatment |
| Self-reported depression: BDI-II | Self-reported depression, measured using the Beck Depression Inventory-II (BDI-II). Higher scores correspond to more depressive symptoms. The minimum total score is 0 points, the maximum total score is 63 points. | From enrollment to the end of iTBS-treatment |
| Self-reported depression at 4-week follow-up: BDI-II | Self-reported depression, measured using the Beck Depression Inventory-II (BDI-II). Higher scores correspond to more depressive symptoms. The minimum total score is 0 points, the maximum total score is 63 points. | From enrollment to 4 weeks after the end of iTBS-treatment |
| Self-rated gesture perception and production: BAG | Change in self-rated gesture perception and production, measured using the Brief Assessment of Gestures (BAG) questionnaire. Higher BAG scores correspond to greater engagement with or reliance on gestures in communication and indicate stronger tendencies to produce or perceive gestures effectively in different contexts. The minimum total score is 12 points, the maximum total score is 60 points. | From enrollment to the end of iTBS-treatment |
| Self-rated gesture perception and production at 4-week follow-up: BAG | Change in self-rated gesture perception and production, measured using the Brief Assessment of Gestures (BAG) questionnaire. Higher BAG scores correspond to greater engagement with or reliance on gestures in communication and indicate stronger tendencies to produce or perceive gestures effectively in different contexts. The minimum total score is 12 points, the maximum total score is 60 points. | From enrollment to 4 weeks after the end of iTBS-treatment |
| Epigenetic changes of neurotrophic and immunological factors | Exploratory molecular biological investigations focusing on neurotrophic (e.g., BDNF, VEGF, GDNF) and immunological (e.g., TNF-alpha, IL-6, t-PA, S100A10) factors. | From enrollment to the end of iTBS treatment |
| Epigenetic changes of neurotrophic and immunological factors at 4-week follow-up | Exploratory molecular biological investigations focusing on neurotrophic (e.g., BDNF, VEGF, GDNF) and immunological (e.g., TNF-alpha, IL-6, t-PA, S100A10) factors. | From enrollment to 4 weeks after the end of iTBS treatment |
| Concentrations of markers of neuronal damage | Concentrations of markers of neuronal damage (e.g., NSE, S100-β) in serum. | From enrollment to the end of iTBS treatment |
| Concentrations of markers of neuronal damage at 4-week follow-up | Concentrations of markers of neuronal damage (e.g., NSE, S100-β) in serum. | From enrollment to 4 weeks after the end of iTBS treatment |