Major Depressive DisorderTBS-DNCT04392947
Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation
A study testing Transcranial Magnetic Stimulation in people with Major Depressive Disorder, run by University Hospital Tuebingen at 7 sites in Germany.
Trial summary
This is a randomized, double-blind, sham-controlled multicenter clinical trial. The aim is to provide evidence for efficacy of TBS in the treatment of patients with major depression. There will be a direct comparison between combined cTBS/iTBS with sham TBS. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 238 participants
- Where
- 7 sitesGermany
- Study dates
- 29 Sep 2020to 31 Jul 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- moderate or severe unipolar depression diagnosed according to criteria of Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)
- duration of the current episode must be ≥ 6 weeks and ≤ 2 years
- HDRS17 ≥ 18
- mild to moderate treatment resistance according to the Antidepressant Treatment History Form [ATHF-SF]. Treatment resistance is defined as having failed at least one but no more than three adequate antidepressant treatments in this episode
- stable antidepressive medication 4 weeks before treatment or no antidepressive treatment
- no further relevant psychiatric axis-I and/or axis-II disorder except for anxiety disorders (according to DSM-5 and SCID-5-PD)
- no comorbid psychotic symptoms
- ability to give consent
Who cannot join
- acute suicidality (MADRS item 10 score > 4)
- antiepileptic drugs and/or benzodiazepines corresponding to > 1mg lorazepam / day
- history of brain surgery, significant and clinically relevant brain malformation or neoplasm, head injury, stroke, dementia or other neurodegenerative disorder
- history of seizures
- previous rTMS treatment
- lifetime history of non-response to adequate electroconvulsive therapy (minimum of eight treatments)
Show all 11Show fewer
- deep brain stimulation
- cardiac pacemakers, intracranial implant, or metal in the cranium
- substance dependence or abuse in the past 3 months (with the exception of tobacco)
- severe somatic comorbidity as judged by the study physician
- pregnancy
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Germany7 sites
Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Bezirkskrankenhaus Augsburg
Augsburg, 86156
University of Leipzig, Dept. Psychiatry and Psychotherapy
Leipzig
University of Munich
Munich, 80336
University of Regensburg, Dept. Psychiatry and Psychotherapy
Regensburg, 93053
University of Tuebingen, Dept Psychiatry and Psychotherapy
Tübingen, 72076
University of Um, Dept. Psychiatry and Psychotherapy
Ulm, 89075
University of Wuerzburg, Dept. Psychiatry and Psychotherapy
Würzburg
About this study
This is a randomized, double-blind, sham-controlled multicenter clinical trial. The aim is to provide evidence for efficacy of TBS in the treatment of patients with major depression. There will be a direct comparison between combined cTBS/iTBS with sham TBS. Overall, 236 patients with major depression will be randomized either to active TBS or sham TBS in a 1:1 ratio. The planned stimulation paradigms will be applied as add-on therapy to standard therapy (antidepressive medication and / or psychotherapy). Patients will receive 30 stimulation sessions in a 6-week treatment period (one session daily from Monday to Friday). Follow up assessments are scheduled 1 and 3 months after end of treatment period.
- Conditions
- Major Depressive Disorder
- Being tested
- Transcranial Magnetic Stimulation, Sham Transcranial Magnetic Stimulation
- Keywords
- major depression, theta burst stimulation, dorsolateral prefrontal cortex, randomized, sham-controlled, multicenter
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic StimulationDevice
MagVenture Coil Cool B70 A/P
Sham Transcranial Magnetic StimulationDevice
MagVenture Coil Cool B70 A/P without TMS being actively delivered
| Study group | Role | What they receive |
|---|---|---|
| combined iTBS/cTBS | Active comparator | Combined theta burst stimulation (TBS) of the left (intermittent TBS, iTBS) and right (continuous TBS, cTBS) dorsolateral prefrontal cortex (dlPFC; F3 and F4 according to EEG10/20 system). Each stimulation session will comprise 2 trains of 600 stimuli each applied in bursts of three pulses at 50 Hz given every 200 ms. iTBS will be applied 20 times for 2 s every 10 s. In the same session, stimulation with cTBS will be applied continuously for 40 s. Intensity of iTBS/cTBS will be standardized at 80 % of the resting motor threshold (rMT).
Additionally, patients receive an electrical co-stimulation of the forehead. One electrode is fixed to FZ and the 2nd one is either fixed to the left forehead (iTBS) or the right forehead (cTBS), rectangular aligned to the upper edge of the FZ-electrode with a distance of 0.5 cm. Intensity of the co-stimulation is applied with 50% of TBS-intensity. Receives: Device: Transcranial Magnetic Stimulation |
| sham stimulation | Sham comparator | Setup is identical to combined active iTBS/cTBS but TBS is not actively delivered Receives: Device: Sham Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate of Montgomery-Asberg Depression Rating Scale (MADRS)
MADRS reduction of at least 50% of baseline value after end of treatment period between active combined iTBS / cTBS and the sham condition.
(rater questionnaire; MADRS raw score ranges between 0 and 60; the higher the score, the more severe depression)
Measured: 6 weeks
Secondary outcomes (11)
Remission rate after treatment
Montgomery-Asberg Depression Rating Scale (MADRS) </= 10 after treatment (rater questionnaire; MADRS raw score ranges between 0 and 60; the higher the score, the more severe depression)
Measured: 6 weeks
Reduction of raw score: Montgomery-Asberg Depression Rating Scale (MADRS)
The reduction of the raw score after treatment will be compared between active TBS and sham TBS (rater questionnaire; range between 0 and 60; higher score indicates higher level of severity)
Measured: 6 weeks
Reduction of raw score: Hamilton Depression Rating Scale 17 items (HDRS17)
The reduction of the raw score after treatment will be compared between active TBS and sham TBS (rater questionnaire; score ranges from 0-53;higher score indicates higher level of severity)
Measured: 6 weeks
Reduction of raw score: Clinical Global Impression (CGI)
The reduction of the raw score after treatment will be compared between active TBS and sham TBS (rater questionnaire; score ranges from 0-7; higher score indicates higher level of severity)
Measured: 6 weeks
Reduction of raw score: Beck Depression Inventory (BDI-II)
The reduction of the raw score during follow-up will be compared between active TBS and sham TBS (self-rating questionnaire; score ranges from 0-63; higher score indicates higher level of severity)
Measured: 10 and 18 weeks
Reduction of raw score: WHO-5 well-being index
The reduction of the raw score during follow-up will be compared between active TBS and sham TBS (self-rating questionnaire; score ranges from 0-25; lower score indicates higher level of severity)
Measured: 10 and 18 weeks
Work Productivity and Activity Impairment Questionnaire (WPAI)
Functionality will be assessed by Work Productivity and Activity Impairment Questionnaire (WPAI; self-rating questionnaire) at baseline, after treatment period as well as during follow-up; contains 6 questions about the effect of health problems on the ability to work and perform regular activities. Health problems are defined as any physical or emotional problem or symptom. Patients are asked to fill in the blanks or circle a number; there is no overall score;
Measured: 6 and 18 weeks
Frequency of adverse events
Comparison of both arms in respect to number of adverse events during treatment period
Measured: 6 weeks
Deterioration rate after treatment period
Deterioration is defined as an increase of MADRS (Montgomery-Asberg Depression Rating Scale) score of 25% compared to baseline score (rater questionnaire; range between 0 and 60; higher score indicates higher level of severity)
Measured: 6 weeks
Examination of the influence of Childhood Trauma Questionnaire (CTQ) at baseline as possible predictor for change of MADRS
It will be examined whether the CTQ can be used for predicting treatment effect, measured by Montgomery-Asberg Depression Rating Scale (MADRS, see above)
Measured: 6 weeks
Examination of the influence of cognitive performance at baseline as possible predictor for change of MADRS
It will be examined whether cognitive performance measured by THINC-Integrated Tool (Thinc-it -tool; includes 4 different test covering different aspects of cognition) at baseline can be used for predicting treatment effect, measured by Montgomery-Asberg Depression Rating Scale (MADRS, see above)
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2020
- Study start29 Sep 2020
- Primary completion28 May 2025
- Study completion31 Jul 2025
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 Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe sponsor's other registered studies.
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 238 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Collaborators
- Federal Ministry of Health, Germany, Institute of Clinical Epidemiology and applied Biometry, University Tuebingen, Germany, Center of Clinical Trials, University Tuebingen, Germany, University of Ulm, University of Regensburg, University of Wuerzburg, Ludwig-Maximilians - University of Munich, Department of Psychiatry and Psychotherapy, University Leipzig, Germany, Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Bezirkskrankenhaus Augsburg, Germany
- Responsible party
- Sponsor
- Investigators
- Christian Plewnia, Prof., MD, Principal investigator, Department of Psychiatry and Psychotherapy, University of Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04392947
- Sponsor's protocol ID
- 01KG2003 BMBF
- Acronym
- TBS-D
- Status last verified
- Oct 2024
- First submitted
- 8 May 2020
- Last updated
- 17 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Plewnia C, Brendel B, Schwippel T, Nieratschker V, Ethofer T, Kammer T, Padberg F, Martus P, Fallgatter AJ. Treatment of major depressive disorder with bilateral theta burst stimulation: study protocol for a randomized, double-blind, placebo-controlled multicenter trial (TBS-D). Eur Arch Psychiatry Clin Neurosci. 2021 Oct;271(7):1231-1243. doi: 10.1007/s00406-021-01280-w. Epub 2021 Jun 19.
PubMed 34146143
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation
- ClinicalTrials.gov ID
- NCT04392947
- Acronym / sponsor ID
- TBS-D / 01KG2003 BMBF
- Conditions
- Major Depressive Disorder
- Keywords
- major depression, theta burst stimulation, dorsolateral prefrontal cortex, randomized, sham-controlled, multicenter
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 238 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Collaborators
- Federal Ministry of Health, Germany, Institute of Clinical Epidemiology and applied Biometry, University Tuebingen, Germany, Center of Clinical Trials, University Tuebingen, Germany, University of Ulm, University of Regensburg, University of Wuerzburg, Ludwig-Maximilians - University of Munich, Department of Psychiatry and Psychotherapy, University Leipzig, Germany, Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Bezirkskrankenhaus Augsburg, Germany
- Study start
- 29 Sep 2020 (actual)
- Primary completion
- 28 May 2025 (actual)
- Study completion
- 31 Jul 2025 (actual)
- First posted
- 19 May 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.
This is a randomized, double-blind, sham-controlled multicenter clinical trial. The aim is to provide evidence for efficacy of TBS in the treatment of patients with major depression. There will be a direct comparison between combined cTBS/iTBS with sham TBS. Overall, 236 patients with major depression will be randomized either to active TBS or sham TBS in a 1:1 ratio. The planned stimulation paradigms will be applied as add-on therapy to standard therapy (antidepressive medication and / or psychotherapy). Patients will receive 30 stimulation sessions in a 6-week treatment period (one session daily from Monday to Friday). Follow up assessments are scheduled 1 and 3 months after end of treatment period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| combined iTBS/cTBS | Active comparator | Device: Transcranial Magnetic StimulationCombined theta burst stimulation (TBS) of the left (intermittent TBS, iTBS) and right (continuous TBS, cTBS) dorsolateral prefrontal cortex (dlPFC; F3 and F4 according to EEG10/20 system). Each stimulation session will comprise 2 trains of 600 stimuli each applied in bursts of three pulses at 50 Hz given every 200 ms. iTBS will be applied 20 times for 2 s every 10 s. In the same session, stimulation with cTBS will be applied continuously for 40 s. Intensity of iTBS/cTBS will be standardized at 80 % of the resting motor threshold (rMT). Additionally, patients receive an electrical co-stimulation of the forehead. One electrode is fixed to FZ and the 2nd one is either fixed to the left forehead (iTBS) or the right forehead (cTBS), rectangular aligned to the upper edge of the FZ-electrode with a distance of 0.5 cm. Intensity of the co-stimulation is applied with 50% of TBS-intensity. |
| sham stimulation | Sham comparator | Device: Sham Transcranial Magnetic StimulationSetup is identical to combined active iTBS/cTBS but TBS is not actively delivered |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- moderate or severe unipolar depression diagnosed according to criteria of Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)
- duration of the current episode must be ≥ 6 weeks and ≤ 2 years
- HDRS17 ≥ 18
- mild to moderate treatment resistance according to the Antidepressant Treatment History Form [ATHF-SF]. Treatment resistance is defined as having failed at least one but no more than three adequate antidepressant treatments in this episode
- stable antidepressive medication 4 weeks before treatment or no antidepressive treatment
Key exclusion criteria (11 listed)
- acute suicidality (MADRS item 10 score > 4)
- antiepileptic drugs and/or benzodiazepines corresponding to > 1mg lorazepam / day
- history of brain surgery, significant and clinically relevant brain malformation or neoplasm, head injury, stroke, dementia or other neurodegenerative disorder
- history of seizures
- previous rTMS treatment
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 |
|---|---|---|
| Transcranial Magnetic StimulationMagVenture Coil Cool B70 A/P | Device | combined iTBS/cTBS |
| Sham Transcranial Magnetic StimulationMagVenture Coil Cool B70 A/P without TMS being actively delivered | Device | sham stimulation |
Primary outcome
Response rate of Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: 6 weeks
MADRS reduction of at least 50% of baseline value after end of treatment period between active combined iTBS / cTBS and the sham condition. (rater questionnaire; MADRS raw score ranges between 0 and 60; the higher the score, the more severe depression)
11 secondary outcomes
Remission rate after treatment
Time frame: 6 weeks
Reduction of raw score: Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: 6 weeks
Reduction of raw score: Hamilton Depression Rating Scale 17 items (HDRS17)
Time frame: 6 weeks
Reduction of raw score: Clinical Global Impression (CGI)
Time frame: 6 weeks
Reduction of raw score: Beck Depression Inventory (BDI-II)
Time frame: 10 and 18 weeks
Reduction of raw score: WHO-5 well-being index
Time frame: 10 and 18 weeks
Work Productivity and Activity Impairment Questionnaire (WPAI)
Time frame: 6 and 18 weeks
Frequency of adverse events
Time frame: 6 weeks
Deterioration rate after treatment period
Time frame: 6 weeks
Examination of the influence of Childhood Trauma Questionnaire (CTQ) at baseline as possible predictor for change of MADRS
Time frame: 6 weeks
Examination of the influence of cognitive performance at baseline as possible predictor for change of MADRS
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2025.
- Derived from this study: PubMed 34146143Plewnia C, Brendel B, Schwippel T, Nieratschker V, Ethofer T, Kammer T, Padberg F, Martus P, Fallgatter AJ. Treatment of major depressive disorder with bilateral theta burst stimulation: study protocol for a randomized, double-blind, placebo-controlled multicenter trial (TBS-D). Eur Arch Psychiatry Clin Neurosci. 2021 Oct;271(7):1231-1243. doi: 10.1007/s00406-021-01280-w. Epub 2021 Jun 19.
- This link is related to the published study protocolLink provided by the sponsor.
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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.
Christian Plewnia, Prof., MD principal investigator
Department of Psychiatry and Psychotherapy, University of Tuebingen
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation in people with Major Depressive Disorder, run by University Hospital Tuebingen at 7 sites in Germany.
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 8 inclusion and 11 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: finished, as of the sponsor's last update on 17 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 7 sites in 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Response rate of Montgomery-Asberg Depression Rating Scale (MADRS) (time frame: 6 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 NCT04392947, 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 17 Sep 2025.