Clinical trial NCT04318977: rTMS Add on Value for Amelioration of Negative Symptoms of Schizophrenia
Official title: rTMS Add on Value for Amelioration of Negative Symptoms of Schizophrenia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Negative Symptoms With Primary Psychotic Disorder
Schizophrenia
Lead sponsor: University of Regensburg
Sponsor class: OTHER
Collaborators: name: University Hospital, Aachen
name: University Hospital Ostrava
name: Brno University Hospital
First posted: 2020-03-24
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized controlled trial with two active and one placebo arm
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Scale for the Assessement of Negative Symptoms (SANS)
timeFrame: 4 weeks
Secondary outcomes:
measure: Scale for the Assessement of Negative Symptoms (SANS)
timeFrame: 2 weeks, 4 weeks, 12 weeks
measure: Positive and Negative syndrome scale (PANSS)
timeFrame: 2 weeks, 4 weeks, 12 weeks
measure: Calgary Depression Scale for Schizophrenia (CDSS)
timeFrame: 2 weeks, 4 weeks, 12 weeks
measure: Clinical global impression (CGI)
timeFrame: 2 weeks, 4 weeks, 12 weeks
measure: Major Depression Inventory (MDI)
timeFrame: 2 weeks, 4 weeks, 12 weeks
measure: Hamilton depression rating scale (HDRS)
timeFrame: 2 weeks, 4 weeks, 12 weeks
measure: Memory span test (digit span)
timeFrame: 4 weeks, 12 weeks
measure: test of attention (d2)
timeFrame: 4 weeks, 12 weeks
measure: Resting state electroencephalogram (EEG)
timeFrame: 4 weeks
measure: magnetic resonance imaging (MRI)
timeFrame: 4 weeks
measure: cigarettes
timeFrame: 4 weeks, 12 weeks
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: Brno University Hospital
city: Ostrava
country: Czechia
facility: University Hospital Ostrava
city: Aachen
country: Germany
facility: University Hospital Aachen
city: Regensburg
country: Germany
facility: University of Regensburg
Study officials:
affiliation: University of Regensburg
name: Berthold Langguth, MD, PhD
role: STUDY_CHAIR
References:
citation: Hebel T, Langguth B, Schecklmann M, Schoisswohl S, Staudinger S, Schiller A, Ustohal L, Sverak T, Horky M, Kasparek T, Skront T, Hyza M, Poeppl TB, Riester ML, Schwemmer L, Zimmermann S, Sakreida K. Rationale and study design of a trial to assess rTMS add-on value for the amelioration of negative symptoms of schizophrenia (RADOVAN). Contemp Clin Trials Commun. 2022 Jan 20;26:100891. doi: 10.1016/j.conctc.2022.100891. eCollection 2022 Apr.