Negative Symptoms With Primary Psychotic Disorder, Schizophrenia
Conditions
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, an interim analysis after inclusion of at least 15 patients in each arm was added 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), the trial will be terminated.
Interventions
DEVICEhigh-frequency rTMS
repetitive transcranial magnetic stimulation
DEVICETBS
theta burst stimulation
DEVICEplacebo
placebo transcranial magnetic stimulation
Sponsors
University Hospital, Aachen
University Hospital Ostrava
Brno University Hospital
University of Regensburg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
randomized controlled trial with two active and one placebo arm
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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)
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Calgary Depression Scale for Schizophrenia (CDSS) | 2 weeks, 4 weeks, 12 weeks | Calgary Depression Scale for Schizophrenia |
| 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 |
| 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 |
| test of attention (d2) | 4 weeks, 12 weeks | test of attention for measurement of concentration |
| Resting state electroencephalogram (EEG) | 4 weeks | measurement of resting state electrophysiologic activity as indicated by frequency analysis and rTMS-evoked activity |
| magnetic resonance imaging (MRI) | 4 weeks | structural, anatomical, diffusion weighted magnetic resonance imaging |
| cigarettes | 4 weeks, 12 weeks | number of smoked cigarettes per week |
| Memory span test (digit span) | 4 weeks, 12 weeks | test for short-term and working memory |
Countries
Czechia, Germany
Outcome results
None listed