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NCT Number: NCT06740747

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

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.

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Key information

Conditions

Schizophrenia Patients Mental Disorders Schizophrenia Schizophrenia Spectrum and Other Psychotic Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hannover Medical School

Hanover, Lower Saxony, 30625, Germany

Location status: Recruiting

Location contact

Rasmus Schülke, MD (Dr. med.)

CONTACT

[email protected]

+49 511 532 2039

Rasmus Schülke, MD (Dr. med.)

PRINCIPAL_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Intermittent theta-burst stimulation

Device

Intermittent theta-burst stimulation, applied sequentially to the cerebellar vermis and the left dorsolateral prefrontal cortex

Sham intermittent theta-burst stimulation

Device

Sham intermittent theta-burst stimulation, applied sequentially to the cerebellar vermis and the left dorsolateral prefrontal cortex

Primary outcomes

  1. Change in negative symptoms

    Time frame: 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 outcomes

  1. Change in negative symptoms at 4-week follow-up

    Time frame: 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.

  2. Speech-gesture rating task

    Time frame: From enrollment to the end of iTBS treatment

    Accuracy and speed of evaluations in the Speech-Gesture Rating Task.

  3. Speech-gesture rating task at 4-week follow-up

    Time frame: 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.

  4. Eye-Tracking Task

    Time frame: From enrollment to the end of iTBS treatment

    Changes in eye movements in the Eye-Tracking Task.

  5. Eye-Tracking Task at 4-week follow-up

    Time frame: 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.

  6. 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.

  7. 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

    Reading the Mind in the Eyes Test at 4-week follow-up.

  8. N-Back Test

    Time frame: From enrollment to the end of iTBS treatment

    Working memory performance in the N-Back Test (sensitivity index).

  9. N-Back Test at 4-week follow-up

    Time frame: 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.

  10. FMRI: Resting-state functional connectivity

    Time frame: 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.

  11. FMRI: Resting-state functional connectivity at 4-week follow-up

    Time frame: 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.

  12. FMRI: Task-related functional connectivity

    Time frame: 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.

  13. FMRI: Task-related functional connectivity at 4-week follow-up

    Time frame: 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.

  14. Inflammatory cytokines

    Time frame: From enrollment to the end of iTBS treatment

    Concentrations of inflammatory cytokines (especially IL-6 and TNF-α) in serum and saliva.

  15. Inflammatory cytokines at 4-week follow-up

    Time frame: 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.

  16. Stimulation-associated perceptions

    Time frame: 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.

  17. Therapy dropout rate

    Time frame: From the beginning of iTBS treatment to the end of iTBS treatment

    Therapy dropout rate (i.e. study termination).

  18. Serious Adverse Events (SAEs)

    Time frame: From the beginning of iTBS treatment to the end of iTBS treatment

    Serious Adverse Events (SAEs), measured using TMSensQ (Section V).

  19. Self-reported depression: BDI-II

    Time frame: 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.

  20. Self-reported depression at 4-week follow-up: BDI-II

    Time frame: 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.

  21. Self-rated gesture perception and production: BAG

    Time frame: 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.

  22. Self-rated gesture perception and production at 4-week follow-up: BAG

    Time frame: 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.

  23. Epigenetic changes of neurotrophic and immunological factors

    Time frame: 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.

  24. Epigenetic changes of neurotrophic and immunological factors at 4-week follow-up

    Time frame: 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.

  25. Concentrations of markers of neuronal damage

    Time frame: From enrollment to the end of iTBS treatment

    Concentrations of markers of neuronal damage (e.g., NSE, S100-β) in serum.

  26. Concentrations of markers of neuronal damage at 4-week follow-up

    Time frame: From enrollment to 4 weeks after the end of iTBS treatment

    Concentrations of markers of neuronal damage (e.g., NSE, S100-β) in serum.

Study contacts

Contact information is provided by the study sponsor or research team.

Rasmus Schülke, MD (Dr. med.)

CONTACT

[email protected]

+49 511 532 2039

Sponsors and collaborators

Lead sponsor

Hannover Medical School

Other

Registry information

Official study title

Intermittierende Theta-Burst-Stimulation Zur Verbesserung Von Negativsymptomatik Und Kognition Bei Schizophrenie

Acronym: ITBS-NKS-2024

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Dec 18, 2024
Registry last updated
Jul 20, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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