rTMS Add on Value for Amelioration of Negative Symptoms of Schizophrenia
- Conditions
- SchizophreniaNegative Symptoms With Primary Psychotic Disorder
- Interventions
- Device: high-frequency rTMSDevice: TBSDevice: placebo
- Registration Number
- NCT04318977
- Lead Sponsor
- University of Regensburg
- Brief Summary
Treatment of depression with repetitive transcranial magnetic stimulation (rTMS) has shown high evidence using high-frequency left dorsolateral prefrontal cortex (DLPFC) stimulation. The treatment of negative symptoms with the same protocol in schizophrenia is considered as possible effective. Theta burst stimulation is a new protocol which is characterized by shorter sessions showing first evidence that it's efficacy is comparable to the high-frequency rTMS. In this randomized placebo-controlled study the efficacy of high-frequency rTMS and TBS are evaluated.
- Detailed Description
In this randomized placebo-controlled study the efficacy of high-frequency rTMS and TBS are evaluated. The active study arms are high-frequency rTMS and iTBS of the left dorsolateral prefrontal cortex to treat negative symptoms in schizophrenia. The control arm will include the same number of patients as each active arm and includes both sham rTMS and sham iTBS in the same proportion as the active treatments.
Standards of the trial will be harmonized across four clinical centers with the aim to pool data for analysis. Each center is responsible for ethical approval and adherence to good clinical practice by itself (Sponsor).
Interim analysis: Several meta-analyses of the effect of rTMS/iTBS on negative symptoms in schizophrenia showing heterogeneous effect sizes have been published since begin of the trial. Thefore, we added an interim analysis after inclusion of at least 15 patients in each arm to the protocol. In case of null findings and low effect sizes (no differences of either rTMS or TBS vs. sham in the primary outcome), we would terminate the trial.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
- ICD-10: schizophrenia with primarily negative symptoms
- Age: 18-75 years
- at least 35 Points at the composite score of the SANS
- stabe medication during the last 2 weeks (at the investigator's discretion)
- written informed consent (by the patient or guardian)
- clinically relevant unstable concomitant somatic diseases
- previous treatment by rTMS
- conditions in which TMS may not be applicated, as e.g., cardiac pacemakers or ferromagnetic implants
- history of epileptic seizures
- current substance or alcohol abuse, or clinically relevant comorbidity (according to M.I.N.I. interview)
- unacceptable concomitant medication (benzodiazepines in higher doses, e.g., Lorazepam > 2 mg/d, Diazepam > 10 mg/d)
- insufficient knowledge of the language of the country of the treatment site
- pregnancy and nursing period
- current statutory hospitalisation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description high-frequency repetitive transcranial magnetic stimulation high-frequency rTMS repetitive transcranial magnetic stimulation over left dorsolateral prefrontal cortex using 3000 pulses applied with 10Hz and 120% resting motor threshold theta burst stimulation TBS intermittent theta burst stimulation over left dorsolateral prefrontal cortex using 600 pulses applied in trains of 10 triplets/bursts (50Hz) with 8s intertrain-interval and 120% resting motor threshold sham rTMS placebo half of the patients with high-frequency repetitive transcranial magnetic stimulation and half of the patients with theta burst Stimulation with angled coil (45 degree) or sham coil
- Primary Outcome Measures
Name Time Method Scale for the Assessement of Negative Symptoms (SANS) 4 weeks negative symptoms in schizophrenia with 25 items and a range 0-125 with higher score representing more symptoms
- Secondary Outcome Measures
Name Time Method Memory span test (digit span) 4 weeks, 12 weeks test for short-term and working memory
cigarettes 4 weeks, 12 weeks number of smoked cigarettes per week
Calgary Depression Scale for Schizophrenia (CDSS) 2 weeks, 4 weeks, 12 weeks Calgary Depression Scale for Schizophrenia
Resting state electroencephalogram (EEG) 4 weeks measurement of resting state electrophysiologic activity as indicated by frequency analysis and rTMS-evoked activity
Positive and Negative syndrome scale (PANSS) 2 weeks, 4 weeks, 12 weeks positive and negative symptoms in schizophrenia with 30 items and a range 30-210 with higher scores representing more symptoms (total score, score for positive, negative symptoms and for general psychopathology)
test of attention (d2) 4 weeks, 12 weeks test of attention for measurement of concentration
Major Depression Inventory (MDI) 2 weeks, 4 weeks, 12 weeks measurment of depressivity: 10 items with a range 0-50 and higher values indicating higher scores
Hamilton depression rating scale (HDRS) 2 weeks, 4 weeks, 12 weeks measurment of depressivity: 21 items with a range 0-65 and higher values indicating higher scores
Scale for the Assessement of Negative Symptoms (SANS) 2 weeks, 4 weeks, 12 weeks negative symptoms in schizophrenia with 25 items and a range 0-125 with higher score representing more symptoms
Clinical global impression (CGI) 2 weeks, 4 weeks, 12 weeks measure of overall symptom severity and treatment response on a scale 1-7 with higher scores presenting more symptoms
magnetic resonance imaging (MRI) 4 weeks structural, anatomical, diffusion weighted magnetic resonance imaging
Trial Locations
- Locations (4)
Brno University Hospital
🇨🇿Brno, Czechia
University Hospital Ostrava
🇨🇿Ostrava, Czechia
University Hospital Aachen
🇩🇪Aachen, Germany
University of Regensburg
🇩🇪Regensburg, Germany