rTMS Add on Value for Amelioration of Negative Symptoms of Schizophrenia

NCT ID: NCT04318977

Last Updated: 2025-09-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-01
• Study Completion Date: 2025-12-30

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.

Conditions

Negative Symptoms With Primary Psychotic Disorder; Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

high-frequency repetitive transcranial magnetic stimulation

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

Group Type: EXPERIMENTAL

high-frequency rTMS

Intervention Type: DEVICE

repetitive transcranial magnetic stimulation

theta burst stimulation

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

Group Type: EXPERIMENTAL

TBS

Intervention Type: DEVICE

theta burst stimulation

sham rTMS

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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DEVICE

placebo transcranial magnetic stimulation

Interventions

high-frequency rTMS

repetitive transcranial magnetic stimulation

Intervention Type: DEVICE

TBS

theta burst stimulation

Intervention Type: DEVICE

placebo

placebo transcranial magnetic stimulation

Intervention Type: DEVICE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Aachen

OTHER

Sponsor Role: collaborator

University Hospital Ostrava

OTHER

Sponsor Role: collaborator

Brno University Hospital

OTHER

Sponsor Role: collaborator

University of Regensburg

OTHER

Sponsor Role: lead

Responsible Party

Berthold Langguth, MD, Ph.D.

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Berthold Langguth, MD, PhD

Role: STUDY_CHAIR

University of Regensburg

Locations

Brno University Hospital

Brno, , Czechia

University Hospital Ostrava

Ostrava, , Czechia

University Hospital Aachen

Aachen, , Germany

University of Regensburg

Regensburg, , Germany

Countries

Czechia; Germany

References

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.

Reference Type: DERIVED

PMID: 35128142 (View on PubMed)

Other Identifiers

19-1616-101

Identifier Type: -

Identifier Source: org_study_id