rTMS Add on Value for Amelioration of Negative Symptoms of Schizophrenia (RADOVAN)

University of Regensburg (UR)

Status: Active, not recruiting

Conditions: Schizophrenia; Negative Symptoms With Primary Psychotic Disorder

Treatments: Device: placebo; Device: high-frequency rTMS; Device: TBS

Study type: Interventional

Funder types: Other

Identifiers

NCT04318977

19-1616-101

Details and patient eligibility

About

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.

Full 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.

Enrollment: 62 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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62 participants in 3 patient groups, including a placebo group

high-frequency repetitive transcranial magnetic stimulation

Experimental group

Description:

repetitive transcranial magnetic stimulation over left dorsolateral prefrontal cortex using 3000 pulses applied with 10Hz and 120% resting motor threshold

Treatment:

Device: high-frequency rTMS

theta burst stimulation

Experimental group

Description:

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

Treatment:

Device: TBS

sham rTMS

Placebo Comparator group

Description:

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

Treatment:

Device: placebo