Rationale and study design of a trial to assess rTMS add-on value for the amelioration of negative symptoms of schizophrenia (RADOVAN)

Contemporary Clinical Trials Communications, vol. 26, pp. 100891

Abstract

BACKGROUND: Schizophrenia is a severe and often difficult to treat psychiatric illness. In many patients, negative symptoms dominate the clinical picture. Meta-analysis has suggested moderate, but significant effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on these symptoms. For treatment of depression a much shorter protocol - intermittent theta burst stimulation (iTBS) - has shown to be non-inferior to conventional high-frequency rTMS. This randomized, sham-controlled, rater-blinded clinical trial assesses the effects of conventional HF-rTMS as well as of iTBS of the left dorsolateral prefrontal cortex in comparison with sham. METHODS: The study will be conducted at two psychiatric university hospitals in Germany and at two in the Czech Republic. Assuming an effect size of 0.64 to be detected with a power of 80%, the calculated sample size is 90 patients. Primary outcome will be the difference in the Scale for the Assessment of Negative Symptoms (SANS) score between each active arm and the sham arm at end of treatment.In addition, the trial investigates effects on depressive symptoms, cognitive performance and cigarette smoking. Recording magnetic resonance imaging (MRI) and electroencephalography (EEG) data will serve to assess whether treatment success can be predicted by neural markers and is related to specific neurobiological changes. DISCUSSION: This is a clinical trial directly comparing 10 Hz-rTMS and iTBS in a sham-controlled manner in treating negative symptoms of schizophrenia. If successful, this would present an interesting treatment option for a chronic and severe condition that can be applied at most psychiatric hospitals and only takes up a few minutes per day. TRIAL REGISTRATION NUMBER: This trial has been registered at clinicaltrials.gov, Identifier: NCT04318977. DATA DISSEMINATION: Results from the trial shall be published in peer-reviewed journals and presented at meetings and conferences.

Authors 15

1. Tobias Hebel corresponding

   University Hospital Regensburg

   Affiliation as printed

   Department of Psychiatry and Psychotherapy, Regensburg University Hospital, Universitätsstraße 84, 93053, Regensburg, Germany

2. Berthold Langguth

   University Hospital Regensburg

   Affiliation as printed

   Department of Psychiatry and Psychotherapy, Regensburg University Hospital, Universitätsstraße 84, 93053, Regensburg, Germany

3. Martin Schecklmann

   University Hospital Regensburg

   Affiliation as printed

   Department of Psychiatry and Psychotherapy, Regensburg University Hospital, Universitätsstraße 84, 93053, Regensburg, Germany

4. Stefan Schoisswohl

   University Hospital Regensburg

   Affiliation as printed

   Department of Psychiatry and Psychotherapy, Regensburg University Hospital, Universitätsstraße 84, 93053, Regensburg, Germany

5. Susanne Staudinger

   University Hospital Regensburg

   Affiliation as printed

   Department of Psychiatry and Psychotherapy, Regensburg University Hospital, Universitätsstraße 84, 93053, Regensburg, Germany

6. Axel Schiller

   University Hospital Regensburg

   Affiliation as printed

   Department of Psychiatry and Psychotherapy, Regensburg University Hospital, Universitätsstraße 84, 93053, Regensburg, Germany

7. Libor Ustohal

   Masaryk University · University Hospital Brno · Central European Institute of Technology – Masaryk University

   Affiliation as printed

   Applied Neurosciences Research Group, Central European Institute of Technology, Masaryk University (CEITEC MU), Kamenice 753/5, 625 00, Brno, Czech Republic

   Department of Psychiatry, Masaryk University and University Hospital Brno, Jihlavska 20, 625 00, Brno, Czech Republic

8. Tomáš Svěrák

   Masaryk University · University Hospital Brno

   Affiliation as printed

   Department of Psychiatry, Masaryk University and University Hospital Brno, Jihlavska 20, 625 00, Brno, Czech Republic

9. Marcel Horký

   Masaryk University · University Hospital Brno

   Affiliation as printed

   Department of Psychiatry, Masaryk University and University Hospital Brno, Jihlavska 20, 625 00, Brno, Czech Republic

10. Tomáš Kašpárek

    Masaryk University · University Hospital Brno

    Affiliation as printed

    Department of Psychiatry, Masaryk University and University Hospital Brno, Jihlavska 20, 625 00, Brno, Czech Republic

11. Tomáš Skřont

    University Hospital Ostrava

    Affiliation as printed

    Department of Psychiatry, University Hospital in Ostrava, 17. Listopadu 1790, 708 52, Ostrava, Czech Republic

12. Timm B. Poeppl Aachen Department of Psychiatry, Psychotherapy and Psychosomatics Medical Faculty

    RWTH Aachen University

    Affiliation as printed

    Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen, Pauwelsstraße 30, 52066, Aachen, Germany

13. M.L. Riester Aachen Department of Psychiatry, Psychotherapy and Psychosomatics Medical Faculty

    RWTH Aachen University

    Affiliation as printed

    Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen, Pauwelsstraße 30, 52066, Aachen, Germany

14. Lara Schwemmer Aachen Department of Psychiatry, Psychotherapy and Psychosomatics Medical Faculty

    RWTH Aachen University

    Affiliation as printed

    Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen, Pauwelsstraße 30, 52066, Aachen, Germany

15. Katrin Sakreida Aachen Department of Psychiatry, Psychotherapy and Psychosomatics Medical Faculty

    RWTH Aachen University

    Affiliation as printed

    Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen, Pauwelsstraße 30, 52066, Aachen, Germany