Negative Symptoms With Primary Psychotic DisorderRADOVANNCT04318977
rTMS Add on Value for Amelioration of Negative Symptoms of Schizophrenia
A study testing high-frequency rTMS and TBS in people with Negative Symptoms With Primary Psychotic Disorder and Schizophrenia, run by University of Regensburg at 4 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Negative Symptoms With Primary Psychotic Disorder, Schizophrenia
- What is being tested?
- high-frequency rTMS and TBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 1 Feb 2020to 30 Dec 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
Show all 9Show fewer
- insufficient knowledge of the language of the country of the treatment site
- pregnancy and nursing period
- current statutory hospitalisation
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Czechia2 sites
Brno University Hospital
Brno
University Hospital Ostrava
Ostrava
Germany2 sites
University Hospital Aachen
Aachen
University of Regensburg
Regensburg
About this study
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.
Read the 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.
- Being tested
- high-frequency rTMS, TBS, placebo
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
high-frequency rTMSDevice
repetitive transcranial magnetic stimulation
TBSDevice
theta burst stimulation
placeboDevice
placebo transcranial magnetic stimulation
| Study group | Role | What they receive |
|---|---|---|
| high-frequency repetitive transcranial magnetic stimulation | Experimental | repetitive transcranial magnetic stimulation over left dorsolateral prefrontal cortex using 3000 pulses applied with 10Hz and 120% resting motor threshold Receives: Device: high-frequency rTMS |
| theta burst stimulation | Experimental | 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 Receives: Device: TBS |
| sham rTMS | Placebo comparator | 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 Receives: Device: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 4 weeks
Secondary outcomes (11)
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
Measured: 2 weeks, 4 weeks, 12 weeks
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)
Measured: 2 weeks, 4 weeks, 12 weeks
Calgary Depression Scale for Schizophrenia (CDSS)
Calgary Depression Scale for Schizophrenia
Measured: 2 weeks, 4 weeks, 12 weeks
Clinical global impression (CGI)
measure of overall symptom severity and treatment response on a scale 1-7 with higher scores presenting more symptoms
Measured: 2 weeks, 4 weeks, 12 weeks
Major Depression Inventory (MDI)
measurment of depressivity: 10 items with a range 0-50 and higher values indicating higher scores
Measured: 2 weeks, 4 weeks, 12 weeks
Hamilton depression rating scale (HDRS)
measurment of depressivity: 21 items with a range 0-65 and higher values indicating higher scores
Measured: 2 weeks, 4 weeks, 12 weeks
Memory span test (digit span)
test for short-term and working memory
Measured: 4 weeks, 12 weeks
test of attention (d2)
test of attention for measurement of concentration
Measured: 4 weeks, 12 weeks
Resting state electroencephalogram (EEG)
measurement of resting state electrophysiologic activity as indicated by frequency analysis and rTMS-evoked activity
Measured: 4 weeks
magnetic resonance imaging (MRI)
structural, anatomical, diffusion weighted magnetic resonance imaging
Measured: 4 weeks
cigarettes
number of smoked cigarettes per week
Measured: 4 weeks, 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2020
- Study start1 Feb 2020
- Primary completion14 Aug 2024
- Study completion30 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Negative Symptoms With Primary Psychotic DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized controlled trial with two active and one placebo arm
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Regensburg
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Aachen, University Hospital Ostrava, Brno University Hospital
- Responsible party
- Principal investigator, Berthold Langguth, MD, Ph.D., University of Regensburg
- Investigators
- Berthold Langguth, MD, PhD, Study chair, University of Regensburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04318977
- Sponsor's protocol ID
- 19-1616-101
- Acronym
- RADOVAN
- Status last verified
- Sep 2025
- First submitted
- 16 Mar 2020
- Last updated
- 19 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35128142
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- rTMS Add on Value for Amelioration of Negative Symptoms of Schizophrenia
- ClinicalTrials.gov ID
- NCT04318977
- Acronym / sponsor ID
- RADOVAN / 19-1616-101
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 62 participants (actual)
- Lead sponsor
- University of RegensburgUniversity, hospital or other
- Collaborators
- University Hospital, Aachen, University Hospital Ostrava, Brno University Hospital
- Study start
- 1 Feb 2020 (actual)
- Primary completion
- 14 Aug 2024 (actual)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 24 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- randomized controlled trial with two active and one placebo arm
| Arm | Type | Receives |
|---|---|---|
| high-frequency repetitive transcranial magnetic stimulation | Experimental | Device: high-frequency rTMSrepetitive transcranial magnetic stimulation over left dorsolateral prefrontal cortex using 3000 pulses applied with 10Hz and 120% resting motor threshold |
| theta burst stimulation | Experimental | Device: TBSintermittent 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 |
| sham rTMS | Placebo comparator | Device: placebohalf 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| high-frequency rTMSrepetitive transcranial magnetic stimulation | Device | high-frequency repetitive transcranial magnetic stimulation |
| TBStheta burst stimulation | Device | theta burst stimulation |
| placeboplacebo transcranial magnetic stimulation | Device | sham rTMS |
Primary outcome
Scale for the Assessement of Negative Symptoms (SANS)
Time frame: 4 weeks
negative symptoms in schizophrenia with 25 items and a range 0-125 with higher score representing more symptoms
11 secondary outcomes
Scale for the Assessement of Negative Symptoms (SANS)
Time frame: 2 weeks, 4 weeks, 12 weeks
Positive and Negative syndrome scale (PANSS)
Time frame: 2 weeks, 4 weeks, 12 weeks
Calgary Depression Scale for Schizophrenia (CDSS)
Time frame: 2 weeks, 4 weeks, 12 weeks
Clinical global impression (CGI)
Time frame: 2 weeks, 4 weeks, 12 weeks
Major Depression Inventory (MDI)
Time frame: 2 weeks, 4 weeks, 12 weeks
Hamilton depression rating scale (HDRS)
Time frame: 2 weeks, 4 weeks, 12 weeks
Memory span test (digit span)
Time frame: 4 weeks, 12 weeks
test of attention (d2)
Time frame: 4 weeks, 12 weeks
Resting state electroencephalogram (EEG)
Time frame: 4 weeks
magnetic resonance imaging (MRI)
Time frame: 4 weeks
cigarettes
Time frame: 4 weeks, 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2025.
- Derived from this study: PubMed 35128142Hebel 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Berthold Langguth, MD, PhD study chair
University of Regensburg
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing high-frequency rTMS and TBS in people with Negative Symptoms With Primary Psychotic Disorder and Schizophrenia, run by University of Regensburg at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Czechia, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Scale for the Assessement of Negative Symptoms (SANS) (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04318977, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2025.