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: * Receive 10 sessions of iTBS over the course of 2 weeks * Undergo extensive examination before iTBS treatment, immediately after iTBS treatment and 4 weeks after iTBS treatment. The examination includes assessment of negative symptoms; psychometric assessment of cognition, social cognition, depressive symptoms; functional magnetic resonance imaging; assessment of eye movements; blood and saliva sampling; assessment of adverse events and stimulation associated sensations. 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
60
Intermittent theta-burst stimulation, applied sequentially to the cerebellar vermis and the left dorsolateral prefrontal cortex
Sham intermittent theta-burst stimulation, applied sequentially to the cerebellar vermis and the left dorsolateral prefrontal cortex
Hannover Medical School
Hanover, Lower Saxony, Germany
RECRUITINGChange 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.
Time frame: From enrollment to the end of iTBS treatment
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.
Time frame: From enrollment to follow-up 4 weeks after the end of iTBS treatment
Speech-gesture rating task
Accuracy and speed of evaluations in the Speech-Gesture Rating Task.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From enrollment to 4 weeks after the end of iTBS treatment
N-Back Test
Working memory performance in the N-Back Test (sensitivity index).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From enrollment to 4 weeks after the end of iTBS treatment
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.