rTMS Add on Value for Amelioration of Negative Symptoms of Schizophrenia

Schizophrenia Clinical Trial

— RADOVAN  

Official title:

rTMS Add on Value for Amelioration of Negative Symptoms of Schizophrenia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04318977
• Other study ID #: 19-1616-101
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2020
• Est. completion date: April 30, 2024

Study information

• Verified date: November 2023
• Source: University of Regensburg
• Contact: Tobias Hebel, MD
• Phone: +49-941-941-1250
• Email: tobias.hebel[@]medbo.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: April 30, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Negative Symptoms With Primary Psychotic Disorder
• Psychotic Disorders
• Schizophrenia

Intervention

Device:
• high-frequency rTMS
repetitive transcranial magnetic stimulation
• TBS
theta burst stimulation
• placebo
placebo transcranial magnetic stimulation

Locations

Country	Name	City	State
Czechia	Brno University Hospital	Brno
Czechia	University Hospital Ostrava	Ostrava
Germany	University Hospital Aachen	Aachen
Germany	University of Regensburg	Regensburg

Sponsors (4)

Lead Sponsor	Collaborator
University of Regensburg	Brno University Hospital, University Hospital Ostrava, University Hospital, Aachen

Countries where clinical trial is conducted

Czechia,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Scale for the Assessement of Negative Symptoms (SANS)	negative symptoms in schizophrenia with 25 items and a range 0-125 with higher score representing more symptoms	4 weeks
Secondary	Scale for the Assessement of Negative Symptoms (SANS)	negative symptoms in schizophrenia with 25 items and a range 0-125 with higher score representing more symptoms	2 weeks, 4 weeks, 12 weeks
Secondary	Positive and Negative syndrome scale (PANSS)	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)	2 weeks, 4 weeks, 12 weeks
Secondary	Calgary Depression Scale for Schizophrenia (CDSS)	Calgary Depression Scale for Schizophrenia	2 weeks, 4 weeks, 12 weeks
Secondary	Clinical global impression (CGI)	measure of overall symptom severity and treatment response on a scale 1-7 with higher scores presenting more symptoms	2 weeks, 4 weeks, 12 weeks
Secondary	Major Depression Inventory (MDI)	measurment of depressivity: 10 items with a range 0-50 and higher values indicating higher scores	2 weeks, 4 weeks, 12 weeks
Secondary	Hamilton depression rating scale (HDRS)	measurment of depressivity: 21 items with a range 0-65 and higher values indicating higher scores	2 weeks, 4 weeks, 12 weeks
Secondary	Memory span test (digit span)	test for short-term and working memory	4 weeks, 12 weeks
Secondary	test of attention (d2)	test of attention for measurement of concentration	4 weeks, 12 weeks
Secondary	Resting state electroencephalogram (EEG)	measurement of resting state electrophysiologic activity as indicated by frequency analysis and rTMS-evoked activity	4 weeks
Secondary	magnetic resonance imaging (MRI)	structural, anatomical, diffusion weighted magnetic resonance imaging	4 weeks
Secondary	cigarettes	number of smoked cigarettes per week	4 weeks, 12 weeks