Intermittent Theta-Burst Stimulation to Improve Negative Symptoms and Cognition in Schizophrenia

Not Applicable

Recruiting

• Conditions: Schizophrenia Patients

• Registration Number: NCT06740747
• Lead Sponsor: Hannover Medical School

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-12-14
• Study First Submitted QC: 2024-12-14
• Study First Posted: 2024-12-18
• Status Verified: 2025-01
• Study Start: 2025-01
• Last Update Submitted: 2025-01-27
• Last Update Posted: 2025-01-29
• Primary Completion: 2025-12-31
• Study Completion: 2026-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Diagnosis of schizophrenia (ICD-10: F20.-)
• Age: 18-65 years
• Ability to give informed consent
• Signed informed consent form

Exclusion Criteria

• Any electronic implants
• Non-MRI-compatible metal implants (e.g., pacemaker, cochlear implant, insulin pump, metal fragment injuries, work in the metal-processing industry)
• Non-TMS-compatible metal implants (compatible items include: earrings, piercings, dental fillings, crowns, implants)
• Claustrophobia
• Epilepsy
• History of traumatic brain injury within the last 3 months
• History of stroke
• Active central nervous system (CNS) infection
• History of CNS infection within the last 3 months
• Pregnancy
• Current drug, medication, or alcohol abuse
• Simultaneous participation in another clinical trial
• Planned changes in psychopharmacological medication within the next 2 weeks
• Severe physical illnesses that could endanger the patient, affect the examinations or make the MRI scanning cause additional burden

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in negative symptoms	From enrollment to the end of iTBS treatment	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.

Secondary Outcome Measures

Name	Time	Method
Eye-Tracking Task	From enrollment to the end of iTBS treatment	Changes in eye movements in the Eye-Tracking Task.
Eye-Tracking Task at 4-week follow-up	From enrollment to 4 weeks after the end of iTBS treatment	Changes in eye movements in the Eye-Tracking Task at 4-week follow-up.
Therapy dropout rate	From the beginning of iTBS treatment to the end of iTBS treatment	Therapy dropout rate (i.e. study termination).
Serious Adverse Events (SAEs)	From the beginning of iTBS treatment to the end of iTBS treatment	Serious Adverse Events (SAEs), measured using TMSensQ (Section V).
Self-reported depression: BDI-II	From enrollment to the end of iTBS-treatment	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.
Inflammatory cytokines	From enrollment to the end of iTBS treatment	Concentrations of inflammatory cytokines (especially IL-6 and TNF-α) in serum and saliva.
Inflammatory cytokines at 4-week follow-up	From enrollment to 4 weeks after the end of iTBS treatment	Concentrations of inflammatory cytokines (especially IL-6 and TNF-α) in serum and saliva.
Change in negative symptoms at 4-week follow-up	From enrollment to follow-up 4 weeks after the end of iTBS treatment	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.
Speech-gesture rating task	From enrollment to the end of iTBS treatment	Accuracy and speed of evaluations in the Speech-Gesture Rating Task.
Speech-gesture rating task at 4-week follow-up	From enrollment to follow-up 4 weeks after the end of iTBS treatment	Accuracy and speed of evaluations in the Speech-Gesture Rating Task at 4-week follow-up.
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.
Reading the Mind in the Eyes Test at 4-week follow-up	From enrollment to 4 weeks after the end of iTBS treatment	Reading the Mind in the Eyes Test at 4-week follow-up.
N-Back Test	From enrollment to the end of iTBS treatment	Working memory performance in the N-Back Test (sensitivity index).
N-Back Test at 4-week follow-up	From enrollment to the end of iTBS treatment	Working memory performance in the N-Back Test (sensitivity index) 4 weeks after the end of iTBS treatment.
FMRI: Resting-state functional connectivity	From enrollment to the end of iTBS treatment	Changes in resting-state functional connectivity in functional magnetic resonance imaging. Focus on connectivity between cerebellar vermis and DLPFC.
FMRI: Resting-state functional connectivity at 4-week follow-up	From enrollment to 4 weeks after the end of iTBS treatment	Changes in resting-state functional connectivity in functional magnetic resonance imaging. Focus on connectivity between cerebellar vermis and DLPFC.
FMRI: Task-related functional connectivity	From enrollment to the end of iTBS treatment	Changes in task-related functional connectivity in functional magnetic resonance imaging, for the N-Back-task and the speech-gesture rating task.
FMRI: Task-related functional connectivity at 4-week follow-up	From enrollment to 4 weeks after the end of iTBS treatment	Changes in task-related functional connectivity in functional magnetic resonance imaging, for the N-Back-task and the speech-gesture rating task.
Stimulation-associated perceptions	From the beginning of each iTBS stimulation to after the end of each iTBS stimulation	Stimulation-associated perceptions, measured using the TMS Adverse Events and Associated Sensations Questionnaire (TMSensQ, Section IV), after each iTBS session.
Self-reported depression at 4-week follow-up: BDI-II	From enrollment to 4 weeks after the end of iTBS-treatment	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.
Self-rated gesture perception and production: BAG	From enrollment to the end of iTBS-treatment	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.
Self-rated gesture perception and production at 4-week follow-up: BAG	From enrollment to 4 weeks after the end of iTBS-treatment	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.
Epigenetic changes of neurotrophic and immunological factors	From enrollment to the end of iTBS treatment	Exploratory molecular biological investigations focusing on neurotrophic (e.g., BDNF, VEGF, GDNF) and immunological (e.g., TNF-alpha, IL-6, t-PA, S100A10) factors.
Epigenetic changes of neurotrophic and immunological factors at 4-week follow-up	From enrollment to 4 weeks after the end of iTBS treatment	Exploratory molecular biological investigations focusing on neurotrophic (e.g., BDNF, VEGF, GDNF) and immunological (e.g., TNF-alpha, IL-6, t-PA, S100A10) factors.
Concentrations of markers of neuronal damage	From enrollment to the end of iTBS treatment	Concentrations of markers of neuronal damage (e.g., NSE, S100-β) in serum.
Concentrations of markers of neuronal damage at 4-week follow-up	From enrollment to 4 weeks after the end of iTBS treatment	Concentrations of markers of neuronal damage (e.g., NSE, S100-β) in serum.

Trial Locations

Locations (1)

Hannover Medical School; 🇩🇪 Hannover, Niedersachsen, Germany