Theta-burst rTMS in Schizophrenia to Ameliorate Negative and Cognitive Symptoms (tbTMS_SCH21)

Theta-burst rTMS in Schizophrenia to Ameliorate Negative and Cognitive Symptoms: a Double-blind, Randomized Clinical Trial

The major target of the study is to confirm the safety and efficacy of our augmented protocol of theta-burst TMS in schizophrenia. Our aim is to confirm the beneficial effects of rTMS treatment on multiple aspects of the disorder such as (1) clinical aspect in terms of PANSS, (2) cognitive aspect such as emotion recognition (ER) and working memory (WM) / distractor filtering (DF) performance, and (3) neurobiology in terms of electrophysiology correlates of ER, WM and DF such as ERPs, event related theta synchronization, resting state theta power, and network connectivity. Response prediction to (theta-burst) TB-rTMS will be the exploratory part of the study.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Transcranial Magnetic Stimulation Repetitive
• Intervention / Treatment: Device: repetitive Transcranial Magnetic Stimulation (rTMS)

Detailed Description

Response prediction will be based on spectral slope, individual alpha peak, and frontal alpha asymmetry, calculated from baseline resting-state EEG in the closed-eye condition (the open-eye condition may also be used). Baseline resting-state fMRI will also be used to predict responses.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Hungary
  • Budapest
    • Budapest, Budapest, Hungary, 1083
      • Department of Psychiatry and Psychotherapy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. diagnosis of schizophrenia or schizoaffective disorder;
2. clinically stabilized on antipsychotic: a stable dose of antipsychotic medication for >4 weeks;
3. age 18-60 years, and
4. presence of negative symptoms (based on PANSS): a negative subscore ≥16 points and [one of items N1-N7 scoring ≥4 or two items N1-N7 scoring ≥3]

Exclusion Criteria:

1. any significant neurological illness;
2. mental retardation
3. history of head injury with loss of consciousness for more than 1 hour
4. history of epileptic seizures or epileptic activity on the baseline EEG (evaluated by an expert in clinical EEG and epilepsy),
5. alcohol or drug abuse within the past 3 months, and
6. depressive episode or antidepressant treatment in the past 4 weeks.
7. Severe positive symptoms inferfere with cognitive tests
8. Implanted pacemaker, implanted drug pump, cochlear implant, implanted defibrillator, implanted neurostimulator or any other TMS incompatible implanted metal device
9. Skin surface is severly injured in the stimulated region of the skull
10. Sclerosis multiplex
11. Pregnancy
12. Severe sleep deprivation
13. Severe heart failure
14. Increased intracranial pressure
15. Untreated migrain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Theta-burst rTMS; Theta-burst repetitive transcranial magnetic stimulation	Device: repetitive Transcranial Magnetic Stimulation (rTMS); Theta-burst stimulation
Sham Comparator: Sham stimulation; Sham stimulation of the same location	Device: repetitive Transcranial Magnetic Stimulation (rTMS); Theta-burst stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive and Negative Syndrome Scale, Negative subscore	The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of patients with schizophrenia. It is the gold standard in the treatment monitoring of schizophrenia.The scale has three subscales : positive, negatve and general symptom score. We use the negative subscore as primary outcome. Its minimum and maximum scores are 7 and 49 respectively. Higher values indicate worse outcome.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive functioning/Short-Term Memory - The Digit Span Forward and Backward tests	They will be used to assess working memory. Digits Recalled is the primary outcome measure ranging between 2 and 10. Lower values indicate worse outcome.	4 weeks
Cognitive functioning/Executive functioning - Wisconsin Card Sorting test	The test will be used to measure cognitive flexibility/Executive functioning. Number of persevarative errors is the major outcome variable of the test, its minimum is 0, while it has no theroretical maximum value. Higher values indicate worse outcome. Punishment sensitivity (P) from the reinforcement learning model of WCST will also be used as outcome variable. Its minimum value is 0 and it has no theoretical maximum value. Lower values indicate worse outcome.	4 weeks
Social cognition 1 - The Baron-Cohen 'Reading the Mind in the Eyes Test '	The total score is the primary outcome, which ranges between 0 and 37 points. Lower values indicate worse outcome.	4 weeks
Social cognition 2 - The 'Faux Pas' test.	Measures Theory of Mind (ToM), and the primary outcome measure is the total score, which ranges between 0 and 1. Lower values indicate worse outcome.	4 weeks
Safety in terms of adverse events	Safety in terms of the number of serious adverse events (SAE). A Serious Adverse Event is any untoward medical occurrence that: Results in death; Is life-threatening or; Requires in-patient confinement or prolongation of existing confinement or; Results in persistent or significant disability/incapacity or; Is a congenital anomaly/birth defect.	4 weeks
Facial Emotion Recogniton - Karolinska Directed Emotional Face set	Facial expression recognition task. Subject have to identify emotional expressions from photographs of 8 male and 8 female subjects. The pictures are chosen from Karolinska Directed Emotional Face set. There are 3 photographs from each faces (happy, neutral, and sad). Hit rate is the primary outcome measure, which ranges from 0% to 100%, and lower values indicate worse outcome. A 64-channel high-density EEG is recorded during the task, and ERPs (e.g., n170) are calculated for each emotion condition and EEG channel.	4 weeks

Collaborators and Investigators

• Sponsor: Semmelweis University

Publications and helpful links

General Publications

• Csukly G, Orban-Szigeti B, Suri K, Zsigmond R, Herman L, Simon V, Kabaji A, Bata B, Harsfalvi P, Vass E, Csibri E, Farkas K, Rethelyi J. Theta-burst rTMS in schizophrenia to ameliorate negative and cognitive symptoms: study protocol for a double-blind, sham-controlled, randomized clinical trial. Trials. 2024 Apr 17;25(1):269. doi: 10.1186/s13063-024-08106-9.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2022
• Primary Completion (Actual): March 24, 2026
• Study Completion (Actual): March 24, 2026

Study Registration Dates

• First Submitted: October 19, 2021
• First Submitted That Met QC Criteria: October 20, 2021
• First Posted (Actual): October 29, 2021

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Therapeutics; Magnetic Field Therapy; Transcranial Magnetic Stimulation
• Other Study ID Numbers: TB-rTMS_SCH2021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No